技术领域Technical Field
本发明属于诊断技术领域，具体涉及结直肠癌标志物及其应用。The present invention belongs to the field of diagnostic technology, and in particular relates to colorectal cancer markers and applications thereof.
背景技术Background Art
结直肠癌(Colorectal Cancer，CRC)是目前全球发病率排名第三的癌症，每年约有190万人确诊，占所有癌症确诊率的10.2％。结直肠癌的死亡率在所有癌症中排名第二，占癌症总死亡率的9.4％。早期结直肠癌通常没有明显的症状，但当出现明显症状时，往往表示癌症已经发展到较晚的阶段，且可能已经扩散到附近的淋巴结或器官，并对患者的身体造成了一定影响。因此，结直肠癌的早期筛查和诊断，对于及时采取治疗干预手段，从而提高治疗效果、降低死亡率、提升国民健康水平，尤为重要。Colorectal cancer (CRC) is currently the third most common cancer in the world, with approximately 1.9 million people diagnosed each year, accounting for 10.2% of all cancer diagnoses. The mortality rate of colorectal cancer ranks second among all cancers, accounting for 9.4% of the total cancer mortality rate. Early colorectal cancer usually has no obvious symptoms, but when obvious symptoms appear, it often means that the cancer has developed to a later stage and may have spread to nearby lymph nodes or organs, causing a certain impact on the patient's body. Therefore, early screening and diagnosis of colorectal cancer are particularly important for timely treatment interventions to improve treatment outcomes, reduce mortality, and improve national health levels.
针对结直肠癌的早期检测，目前已有的常见方法包括结肠镜检查、粪便潜血试验、影像学检查等。虽然这些技术已经较为成熟，但仍存在以下局限性：1)肠镜检查依从性低。肠镜检查前的肠道准备和清理时间长，检查过程会引起患者的不适或疼痛，价格相对高，且肠镜检查需要专业医生和设备，医疗资源主要集中在城市医院，增加了患者错过最佳治疗窗口的风险。2)有心血管疾病、凝血障碍、肠穿孔风险的患者不适合进行肠镜检查。For the early detection of colorectal cancer, the common methods currently available include colonoscopy, fecal occult blood test, imaging examination, etc. Although these technologies are relatively mature, they still have the following limitations: 1) Low compliance with colonoscopy. The intestinal preparation and cleaning time before colonoscopy is long, the examination process will cause discomfort or pain to the patient, the price is relatively high, and colonoscopy requires professional doctors and equipment. Medical resources are mainly concentrated in urban hospitals, which increases the risk of patients missing the best treatment window. 2) Patients with cardiovascular disease, coagulation disorders, and risk of intestinal perforation are not suitable for colonoscopy.
液体活检技术的高速发展，为结直肠癌的早筛、诊断提供了新途径。如ctDNA检测技术，通过对肿瘤细胞释放到血液中ctDNA(circulating tumor DNA)片段进行基因组或者甲基化分析，进行结直肠癌的诊断，辅助确定肿瘤的性质、大小和病程进展。ctDNA技术通过非侵入性的方式进行诊断，避免了传统组织切片检查的痛苦和不适。但是，该技术仍存在相当的局限性：1)细胞凋亡或组织损伤产生的DNA片段会干扰ctDNA检测，对ctDNA特异性具有一定影响；2)ctDNA的半衰期仅为2小时1-2，在早期，肿瘤ctDNA在血液中的浓度非常低，导致ctDNA的灵敏度有限；3)转移灶的位置会影响ctDNA的浓度和检测率，仅存在腹膜转移和仅存在肺转移的患者，RAS突变片段较难于此类患者的血浆中检出3。4)ctDNA检测的相关成本不容忽视。The rapid development of liquid biopsy technology has provided a new way for early screening and diagnosis of colorectal cancer. For example, ctDNA detection technology can diagnose colorectal cancer by performing genomic or methylation analysis on ctDNA (circulating tumor DNA) fragments released by tumor cells into the blood, and assist in determining the nature, size and progression of the tumor. ctDNA technology diagnoses in a non-invasive way, avoiding the pain and discomfort of traditional tissue biopsy. However, this technology still has considerable limitations: 1) DNA fragments produced by cell apoptosis or tissue damage will interfere with ctDNA detection and have a certain impact on ctDNA specificity; 2) The half-life of ctDNA is only 2hours1-2 . In the early stage, the concentration of tumor ctDNA in the blood is very low, resulting in limited sensitivity of ctDNA; 3) The location of metastatic lesions will affect the concentration and detection rate of ctDNA. For patients with only peritoneal metastasis and only lung metastasis, RAS mutation fragments are more difficult to detect in the plasma of such patients3.4 ) The associated costs of ctDNA detection cannot be ignored.
1.Lu L,Bi J,Bao L.Genetic profiling of cancer with circulating tumorDNA analysis.J Genet Genomics 2018；45:79–85。1. Lu L, Bi J, Bao L. Genetic profiling of cancer with circulating tumorDNA analysis. J Genet Genomics 2018;45:79–85.
2.Diehl F,Schmidt K,Choti MA,et al.Circulating mutant DNA to assesstumor dynamics.Nat Med 2008；14:985–90。2. Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics. Nat Med 2008;14:985–90.
3.Bando H,Nakamura Y,Taniguchi H,et al.Effects of metastatic sites oncirculating tumor DNA in patients with metastatic colorectal cancer.JCOPrecis Oncol 2022；6:e2100535。3. Bando H, Nakamura Y, Taniguchi H, et al. Effects of metastatic sites oncirculating tumor DNA in patients with metastatic colorectal cancer. JCOPrecis Oncol 2022;6:e2100535.
发明内容Summary of the invention
本发明第一方面的目的，在于提供检测标志物的物质在制备用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的产品中的应用。The purpose of the first aspect of the present invention is to provide the use of a substance for detecting a marker in the preparation of a product for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
本发明第二方面的目的，在于提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的标志物组合。The purpose of the second aspect of the present invention is to provide a marker combination for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
本发明第三方面的目的，在于提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的产品。The purpose of the third aspect of the present invention is to provide a product for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
本发明第四方面的目的，在于提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的模型的构建方法。The purpose of the fourth aspect of the present invention is to provide a method for constructing a model for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
本发明第五方面的目的，在于提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的装置或系统。The purpose of the fifth aspect of the present invention is to provide a device or system for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
本发明第六方面的目的，在于提供一种计算机设备。The sixth aspect of the present invention aims to provide a computer device.
本发明第七方面的目的，在于提供一种计算机可存储介质。The seventh aspect of the present invention aims to provide a computer storable medium.
本发明第八方面的目的，在于提供一种构建结直肠癌模型的方法。The purpose of the eighth aspect of the present invention is to provide a method for constructing a colorectal cancer model.
本发明第九方面的目的，在于提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的方法。The purpose of the ninth aspect of the present invention is to provide a method for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
为了实现上述目的，本发明所采取的技术方案是：In order to achieve the above object, the technical solution adopted by the present invention is:
本发明的第一个方面，提供检测标志物的物质在制备产品中的应用：The first aspect of the present invention provides the use of a substance for detecting a marker in preparing a product:
所述产品用于：结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估；The product is used for: early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer;
所述标志物为A，所述A包含B中的至少一种，即可以是B中1种、2种、3种、4种、5种、6种、7种、8种、9种、10种、11种、12种、13种、14种、15种、16种、17种、18种、19种、20种、21种、22种、23种、24种、25种、26种、27种、28种、29种、30种、31种、32种、33种、34种、35种、36种、37种、38种、39种、40种、41种、42种、43种、44种、45种、46种、47种、48种、49种、50种、51种、52种、53种、54种、55种、56种、57种、58种、59种、60种、61种、62种、63种、64种、65种、66种、67种、68种、69种、70种、71种、72种、73种、74种、75种、76种、77种、78种、79种、80种、81种、82种、83种、84种、85种、86种、87种、88种、89种、或90种；The marker is A, and A includes at least one of B, that is, it can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 of B. , 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90;
所述B为：ADAMTS8、ADGRE1、ADGRE2、ADGRE5、ADGRG2、AGR3、ANGPTL4、AREG、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CEACAM5、CFP、CKAP4、CLEC3B、CNTN1、CNTN4、CNTN5、COMP、CRTAC1、DCC、DLK1、EDA2R、ENPP6、ESM1、EXTL1、FAP、FASLG、FCER2、FCRL1、FGF21、GCG、GDF15、GNAS、GRK5、GSN、HMCN2、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGA11、ITGA2、ITGAM、ITGB1、ITGB7、ITIH3、ITM2A、KRT19、LBP、LMNB2、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PLXDC2、POF1B、PROK1、PTPRS、PTX3、RBFOX3、RET、SELL、SERPINA1、SOD3、SPON2、SPP1、TCL1A、THBS4、TMPRSS15、TNC、TNFRSF10B、TNFRSF11A、VSIG4。The B is: ADAMTS8, ADGRE1, ADGRE2, ADGRE5, ADGRG2, AGR3, ANGPTL4, AREG, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CEACAM5, CFP, CKAP4, CLEC3B, CNTN1, CNTN4, CNTN5 , COMP, CRTAC1, DCC, DLK1, EDA2R, ENPP6, ESM1, EXTL1, FAP, FASLG, FCER2, FCRL1, FGF21, GCG, GDF15, GNAS, GRK5, GSN, HMCN2, IFNL1, IGDCC4, IGFBP1, I GSF3, IL4R, IL6, ITGA11, ITGA2, ITGAM, ITGB1, ITGB7, ITIH3, ITM2A, KRT19, LBP, LMNB2, LPL, MEGF9, MMP12, NOTCH1, NOTCH3, NOS2, NPY, NT5C1A, NTRK2, PCDH7, PGA4, PKD1, PLXDC1, PLXDC2, POF1B, PROK1, PTPRS, PTX3, RBFOX3, RET, SELL, SERPINA1, SOD3, SPON2, SPP1, TCL1A, THBS4, TMPRSS15, TNC, TNFRSF10B, TNFRSF11A, VSIG4.
优选地，所述A包含所述B中的任意1种、2种、3种、4种、5种、6种、7种、或8种。Preferably, the A comprises any 1, 2, 3, 4, 5, 6, 7, or 8 of the Bs.
优选地，所述A包含单marker,所述单marker为所述B中的任意1种，比如：ADAMTS8、ADGRE1、ADGRE2、ADGRE5、ADGRG2、AGR3、ANGPTL4、AREG、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CEACAM5、CFP、CKAP4、CLEC3B、CNTN1、CNTN4、CNTN5、COMP、CRTAC1、DCC、DLK1、EDA2R、ENPP6、ESM1、EXTL1、FAP、FASLG、FCER2、FCRL1、FGF21、GCG、GDF15、GNAS、GRK5、GSN、HMCN2、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGA11、ITGA2、ITGAM、ITGB1、ITGB7、ITIH3、ITM2A、KRT19、LBP、LMNB2、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PLXDC2、POF1B、PROK1、PTPRS、PTX3、RBFOX3、RET、SELL、SERPINA1、SOD3、SPON2、SPP1、TCL1A、THBS4、TMPRSS15、TNC、TNFRSF10B、TNFRSF11A、或VSIG4；其中，SPP1、PTX3、ANGPTL4、C9、GDF15、IGFBP1、CEACAM5、KRT19、MMP12、ESM1、TNFRSF10B、SERPINA1、ITIH3、AREG、LBP、SPON2、NT5C1A、VSIG4、POF1B、PGA4、IL6、ITM2A、IL4R、EDA2R、CCL7、RBFOX3、CKAP4、LMNB2、FGF21、PROK1、TNC、TNFRSF11A、NOS2的含量、表达量和/或活性相对于参考水平提高，TMPRSS15、RET、PLXDC2、ENPP6、FASLG、ITGA11、PLXDC1、ITGAM、PTPRS、COMP、CNTN5、NTRK2、ADGRG2、FCRL1、ITGB1、HMCN2、ADAMTS8、GNAS、CNTN4、TCL1A、ITGB7、CNTN1、CLEC3B、BMP4、GCG、MEGF9、ITGA2、ADGRE5、LPL、SELL、THBS4、FAP、NOTCH1、ADGRE2、DLK1、AGR3、NOTCH3、ASAH2、CEACAM16、GSN、CFP、IGDCC4、NPY、CRTAC1、IGSF3、DCC、PCDH7、BAG3、EXTL1、CD48、ADGRE1、GRK5、IFNL1、PKD1、SOD3、CDH23、FCER2的含量表达量和/或活性相对于参考水平降低，参考水平代表来自未患有结直肠癌的同年龄段待测对象的含量、表达量和/或活性。Preferably, the A comprises a single marker, and the single marker is any one of the B, such as ADAMTS8, ADGRE1, ADGRE2, ADGRE5, ADGRG2, AGR3, ANGPTL4, AREG, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CEACAM5, CFP, CKAP4, CLEC3B, CNTN1, CNTN4, CNTN5, COMP, CRTAC1, DCC, DLK1, EDA2R, ENPP6, ESM1, EXTL1, FAP, FASLG, FCER2, FCRL1, FGF21, GCG, GDF15, GNAS, GRK5, GSN, HMCN2, IFNL1, IGDCC4, I GFBP1, IGSF3, IL4R, IL6, ITGA11, ITGA2, ITGAM, ITGB1, ITGB7, ITIH3, ITM2A, KRT19, LBP, LMNB2, LPL, MEGF9, MMP12, NOTCH1, NOTCH3, NOS2, NPY, NT5C1A, NTRK2, PCDH7, PGA4, PKD1, PLXDC1, PLXDC2, PO F1B, PROK1, PTPRS, PTX3, RBFOX3, RET, SELL, SERPINA1, SOD3, SPON2, SPP1, TCL1A, THBS4, TMPRSS15, TNC, TNFRSF10B, TNFRSF11A, or VSIG4; among them, SPP1, PTX3, ANGPTL4 , C9, GDF15, IGFBP1, CEACAM5, KRT19, MMP12, ESM1, TNFRSF10B, SERPINA1, ITIH3, AREG, LBP, SPON2, NT5C1A, VSIG4, POF1B, PGA4, IL6, ITM2A, IL4R, EDA2R, CCL7, RBFOX3, CKAP4, LMNB2, FGF21, PROK1, TNC, TNFRSF11A, and NOS2, and the content, expression and/or activity of TMPRSS15, RET, PLXDC2, ENPP6, FASLG, ITGA11, PLXDC1, ITGAM, PTPRS, COMP, CNTN5, NTRK2, ADGRG2, FCRL1, ITGB1, The content, expression and/or activity of HMCN2, ADAMTS8, GNAS, CNTN4, TCL1A, ITGB7, CNTN1, CLEC3B, BMP4, GCG, MEGF9, ITGA2, ADGRE5, LPL, SELL, THBS4, FAP, NOTCH1, ADGRE2, DLK1, AGR3, NOTCH3, ASAH2, CEACAM16, GSN, CFP, IGDCC4, NPY, CRTAC1, IGSF3, DCC, PCDH7, BAG3, EXTL1, CD48, ADGRE1, GRK5, IFNL1, PKD1, SOD3, CDH23 and FCER2 are decreased relative to the reference level, and the reference level represents the content, expression and/or activity of the subjects of the same age group who do not have colorectal cancer.
优选地，所述参考水平代表健康的同年龄段待测对象的含量、表达量和/或活性。Preferably, the reference level represents the content, expression level and/or activity of healthy subjects of the same age group.
优选地，所述单marker为：ADGRE1、ADGRE2、AGR3、ANGPTL4、AREG、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CFP、CKAP4、CNTN4、CNTN5、CRTAC1、DCC、DLK1、EDA2R、ESM1、FAP、FCER2、FCRL1、FGF21、GCG、GNAS、GRK5、GSN、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGAM、ITGB1、ITIH3、ITM2A、LBP、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PROK1、PTPRS、RBFOX3、SELL、SERPINA1、SPON2、TCL1A、TNC、TNFRSF10B、TNFRSF11A、或VSIG4。Preferably, the single marker is: ADGRE1, ADGRE2, AGR3, ANGPTL4, AREG, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CFP, CKAP4, CNTN4, CNTN5, CRTAC1, DCC, DLK1, EDA2R, ESM1, FAP, FCER2, FCRL1, FGF21, GCG, GNAS, GRK5, GSN, IFNL1, IGDCC4, IGFB P1, IGSF3, IL4R, IL6, ITGAM, ITGB1, ITIH3, ITM2A, LBP, LPL, MEGF9, MMP12, NOTCH1, NOTCH3, NOS2, NPY, NT5C1A, NTRK2, PCDH7, PGA4, PKD1, PLXDC1, PROK1, PTPRS, RBFOX3, SELL, SERPINA1, SPON2, TCL1A, T NC, TNFRSF10B, TNFRSF11A, or VSIG4.
优选地，所述单marker为：FCRL1、NTRK2、CNTN5、ITGB1、GCG、IL4R、MMP12、TNFRSF10B、ITGAM、RBFOX3、IGFBP1、LBP、ESM1、SERPINA1、SELL、DLK1、C9、PLXDC1、EDA2R、CNTN4、CFP、NOTCH3、TCL1A、LPL、IL6、DCC、PTPRS、BMP4、NT5C1A、ITIH3、ANGPTL4、ASAH2、FAP、GNAS、CKAP4、或AREG。Preferably, the single marker is: FCRL1, NTRK2, CNTN5, ITGB1, GCG, IL4R, MMP12, TNFRSF10B, ITGAM, RBFOX3, IGFBP1, LBP, ESM1, SERPINA1, SELL, DLK1, C9, PLXDC1, EDA2R, CNTN4, CFP, NOTCH3, TCL1A, LPL, IL6, DCC, PTPRS, BMP4, NT5C1A, ITIH3, ANGPTL4, ASAH2, FAP, GNAS, CKAP4, or AREG.
优选地，所述单marker为：AREG、FCRL1、NTRK2、CNTN5、ITGB1、GCG、IL4R、MMP12、或TNFRSF10B。Preferably, the single marker is: AREG, FCRL1, NTRK2, CNTN5, ITGB1, GCG, IL4R, MMP12, or TNFRSF10B.
最优选地，所述单marker为：FCRL1或AREG。Most preferably, the single marker is: FCRL1 or AREG.
优选地，所述A包含2markers组合，所述2markers组合为所述B中的任意2种。Preferably, A comprises a combination of 2 markers, and the combination of 2 markers is any 2 of the combinations in B.
优选地，所述2markers组合为C中的任意2种，所述C为：ADGRE5、ADGRG2、AREG、CEACAM5、CLEC3B、CNTN5、COMP、EDA2R、ENPP6、EXTL1、FASLG、FCRL1、GDF15、HMCN2、ITGA11、ITGA2、ITGAM、ITGB7、KRT19、LMNB2、PLXDC1、PLXDC2、POF1B、PTX3、RET、SELL、SOD3、SPP1、THBS4、TMPRSS15。Preferably, the 2markers combination is any 2 of C, and C is: ADGRE5, ADGRG2, AREG, CEACAM5, CLEC3B, CNTN5, COMP, EDA2R, ENPP6, EXTL1, FASLG, FCRL1, GDF15, HMCN2, ITGA11, ITGA2, ITGAM, ITGB7, KRT19, LMNB2, PLXDC1, PLXDC2, POF1B, PTX3, RET, SELL, SOD3, SPP1, THBS4, TMPRSS15.
优选地，所述2markers组合为：TMPRSS15与GDF15，TMPRSS15与SPP1，TMPRSS15与KRT19，SPP1与ADGRE5，GDF15与ADGRE5，GDF15与COMP，SPP1与COMP，TMPRSS15与POF1B，PTX3与THBS4，TMPRSS15与EDA2R，TMPRSS15与LMNB2，PTX3与HMCN2，PTX3与RET，GDF15与PTX3，TMPRSS15与FASLG，TMPRSS15与ENPP6，COMP与LMNB2，PTX3与ENPP6，GDF15与ADGRG2，THBS4与LMNB2，SPP1与SOD3，PTX3与KRT19，GDF15与PLXDC2，PTX3与POF1B，TMPRSS15与SOD3，TMPRSS15与PTX3，COMP与EDA2R，PLXDC2与POF1B，GDF15与ITGA2，GDF15与HMCN2，TMPRSS15与CEACAM5，TMPRSS15与AREG，PTX3与ADGRG2，GDF15与THBS4，SPP1与CLEC3B，TMPRSS15与FCRL1，RET与SOD3，TMPRSS15与ITGA11，GDF15与RET，HMCN2与SPP1，PTX3与PLXDC2，GDF15与PLXDC1，SPP1与PLXDC1，PTX3与COMP，PTX3与FASLG，PTX3与ITGAM，ITGA11与LMNB2，PLXDC2与SPP1，PTX3与CLEC3B，GDF15与ITGA11，PLXDC2与KRT19，TMPRSS15与THBS4，GDF15与CLEC3B，TMPRSS15与ITGAM，ENPP6与SPP1，PTX3与ITGA2，SPP1与ITGA2，GDF15与ITGAM，PLXDC2与CEACAM5，COMP与KRT19，PTX3与SELL，SPP1与ADGRG2，PTX3与CNTN5，ITGB7与POF1B，PLXDC2与LMNB2，TMPRSS15与SELL，CEACAM5与COMP，KRT19与ITGB7，GDF15与ITGB7，LMNB2与SOD3，TMPRSS15与RET，PTX3与SPP1，POF1B与SOD3，PTX3与SOD3，ADGRG2与LMNB2，TMPRSS15与EXTL1，GDF15与FCRL1，PTX3与FCRL1，ITGA11与POF1B，LMNB2与ITGAM，ITGA11与KRT19，TMPRSS15与ITGA2，PTX3与EXTL1，TMPRSS15与ITGB7，GDF15与CNTN5，TMPRSS15与CLEC3B，PTX3与ITGA11，TMPRSS15与HMCN2，PLXDC2与AREG，TMPRSS15与COMP，THBS4与POF1B，POF1B与ITGA2，LMNB2与ITGB7，TMPRSS15与ADGRG2，KRT19与ADGRE5，CEACAM5与SOD3，TMPRSS15与PLXDC2，THBS4与EDA2R，HMCN2与AREG，HMCN2与POF1B，FCRL1与COMP，SPP1与FCRL1，ENPP6与ITGA11，COMP与POF1B，PTX3与PLXDC1，FCRL1与LMNB2，LMNB2与PLXDC1，KRT19与ITGA2，SPP1与FASLG，ADGRE5与EDA2R，CEACAM5与ITGB7，LMNB2与ADGRE5，PTX3与ITGB7，PTX3与LMNB2，CEACAM5与ITGA11，POF1B与ADGRE5，FASLG与PLXDC1，KRT19与EXTL1，KRT19与FASLG，PLXDC2与ITGA11，ENPP6与EXTL1，FCRL1与SOD3，LMNB2与CLEC3B，GDF15与EXTL1，THBS4与AREG，POF1B与PLXDC1，ENPP6与THBS4，CEACAM5与CLEC3B，PTX3与CEACAM5，RET与FASLG，FCRL1与POF1B，ENPP6与POF1B，与FCRL1，ENPP6与LMNB2，ADGRG2与KRT19，CEACAM5与ITGAM，PTX3与EDA2R，GDF15与ENPP6，SPP1与THBS4，PLXDC2与EDA2R，ENPP6与ADGRE5，KRT19与SELL，FASLG与SOD3，KRT19与SOD3，ENPP6与KRT19，TMPRSS15与CNTN5，SPP1与RET，GDF15与CEACAM5，HMCN2与FASLG，ADGRG2与POF1B，ITGA2与EDA2R，RET与POF1B，CEACAM5与THBS4，TMPRSS15与PLXDC1，COMP与FASLG，RET与LMNB2，CEACAM5与ADGRE5，ENPP6与CEACAM5，CLEC3B与EDA2R，ITGA11与CNTN5，SPP1与EXTL1，ENPP6与COMP，ADGRG2与EDA2R，ITGA11与SOD3，SPP1与SELL，GDF15与SOD3，SPP1与ITGA11，COMP与AREG，PLXDC2与FASLG，RET与CLEC3B，RET与KRT19，CEACAM5与RET，LMNB2与CNTN5，THBS4与KRT19，FCRL1与CLEC3B，LMNB2与ITGA2，HMCN2与CLEC3B，SPP1与ITGB7，POF1B与FASLG，POF1B与EXTL1，KRT19与PLXDC1，HMCN2与CEACAM5，ADGRG2与FASLG，FCRL1与KRT19，PLXDC2与FCRL1，ENPP6与AREG，LMNB2与FASLG，HMCN2与EDA2R，ITGB7与EDA2R，PTX3与ADGRE5，HMCN2与LMNB2，THBS4与RET，PLXDC2与RET，CEACAM5与ADGRG2，PLXDC2与EXTL1，RET与ITGB7，FCRL1与ADGRE5，THBS4与ITGA11，ENPP6与PLXDC1，ITGA11与EDA2R，CEACAM5与FASLG，RET与ITGA2，ENPP6与FASLG，ITGA11与FASLG，COMP与SELL，ENPP6与RET，THBS4与FASLG，ITGA11与COMP，ITGA2与SOD3，ITGA11与SELL，TMPRSS15与ADGRE5，THBS4与CLEC3B，PLXDC2与ITGB7，ITGA11与RET，HMCN2与KRT19，PLXDC1与EDA2R，CEACAM5与EXTL1，FCRL1与THBS4，RET与AREG，FCRL1与EXTL1，POF1B与ITGAM，ENPP6与ITGB7，ADGRG2与AREG，ITGA11与CLEC3B，PLXDC2与ITGAM，CLEC3B与EXTL1，LMNB2与KRT19，CEACAM5与ITGA2，FCRL1与ITGA11，SOD3与AREG，ENPP6与ITGAM，ITGA2与AREG，PLXDC2与ADGRE5，POF1B与CLEC3B，CNTN5与CLEC3B，ENPP6与EDA2R，KRT19与CLEC3B，GDF15与POF1B，PTX3与AREG，FASLG与EXTL1，PLXDC2与COMP，GDF15与KRT19，SOD3与EDA2R，ITGAM与SOD3，KRT19与ITGAM，GDF15与SELL，PLXDC2与CNTN5，CNTN5与AREG，ENPP6与HMCN2，CNTN5与FASLG，FCRL1与ADGRG2，SPP1与LMNB2，CEACAM5与PLXDC1，SPP1与CEACAM5，ADGRG2与RET，CNTN5与EDA2R，ADGRG2与SOD3，ADGRG2与EXTL1，THBS4与CNTN5，ITGB7与AREG，FCRL1与EDA2R，SPP1与CNTN5，GDF15与FASLG，FASLG与ITGA2，ADGRG2与PLXDC1，FCRL1与CNTN5，HMCN2与ITGA11，HMCN2与FCRL1，FCRL1与ITGA2，EXTL1与AREG，ITGA11与EXTL1，FASLG与CLEC3B，CEACAM5与CNTN5，ITGB7与CLEC3B，SPP1与ITGAM，GDF15与SPP1，CNTN5与ADGRE5，FASLG与ITGAM，ADGRG2与CLEC3B，ITGAM与AREG，FCRL1与RET，LMNB2与EXTL1，HMCN2与PLXDC1，FASLG与AREG，SPP1与KRT19，ITGA11与ITGB7，ITGA11与AREG，RET与EXTL1，POF1B与SELL，PLXDC2与HMCN2，CNTN5与PLXDC1，PLXDC2与THBS4，THBS4与EXTL1，KRT19与CNTN5，CEACAM5与EDA2R，FCRL1与ITGB7，CEACAM5与LMNB2，COMP与RET，CNTN5与POF1B，POF1B与EDA2R，FCRL1与FASLG，ITGA2与EXTL1，ITGB7与PLXDC1，ADGRG2与COMP，COMP与EXTL1，PLXDC2与CLEC3B，ENPP6与SOD3，PLXDC2与ITGA2，CNTN5与EXTL1，ITGA11与PLXDC1，ADGRG2与CNTN5，ITGAM与EDA2R，SPP1与POF1B，CLEC3B与ITGA2，ITGB7与FASLG，ITGA11与ADGRE5，PLXDC2与ENPP6，GDF15与LMNB2，CNTN5与SOD3，CNTN5与ITGA2，ITGA11与ADGRG2，HMCN2与CNTN5，CEACAM5与KRT19，RET与ADGRE5，FASLG与ADGRE5，PLXDC2与SOD3，HMCN2与SOD3，SOD3与PLXDC1，EXTL1与SOD3，CEACAM5与SELL，HMCN2与ADGRG2，CEACAM5与POF1B，COMP与ITGA2，ADGRE5与AREG，CLEC3B与ITGAM，FCRL1与CEACAM5，HMCN2与ITGA2，FCRL1与PLXDC1，CLEC3B与ADGRE5，ENPP6与ITGA2，GDF15与AREG，LMNB2与POF1B，HMCN2与ITGAM，ITGB7与EXTL1，HMCN2与EXTL1，LMNB2与SELL，PLXDC2与PLXDC1，FCRL1与ITGAM，ENPP6与CLEC3B，SOD3与SELL，THBS4与ITGAM，COMP与ITGB7，CNTN5与ITGB7，THBS4与SELL，HMCN2与COMP，PLXDC1与SELL，HMCN2与SELL，COMP与CNTN5，ITGB7与ITGA2，PLXDC1与AREG，SPP1与AREG，HMCN2与RET，RET与CNTN5，THBS4与ITGA2，RET与EDA2R，HMCN2与ITGB7，RET与ITGAM，ADGRG2与ITGAM，FCRL1与AREG，THBS4与ITGB7，THBS4与SOD3，AREG与SELL，ITGB7与SOD3，ENPP6与CNTN5，COMP与PLXDC1，ITGA2与SELL，KRT19与EDA2R，HMCN2与ADGRE5，ITGA2与ADGRE5，EXTL1与ITGAM，THBS4与PLXDC1，EXTL1与PLXDC1，GDF15与EDA2R，KRT19与POF1B，RET与PLXDC1，THBS4与ADGRE5，ITGAM与PLXDC1，EXTL1与SELL，COMP与SOD3，ENPP6与SELL，ITGA11与ITGA2，ADGRG2与ITGA2，ENPP6与ADGRG2，ADGRG2与ADGRE5，THBS4与ADGRG2，ITGA11与ITGAM，SPP1与EDA2R，RET与SELL，ADGRG2与ITGB7，COMP与ITGAM，CLEC3B与SOD3，ITGB7与ADGRE5，CNTN5与SELL，PLXDC2与SELL，ITGB7与ITGAM，COMP与CLEC3B，ITGB7与SELL，ITGA2与PLXDC1，FCRL1与SELL，ADGRE5与SOD3，ADGRE5与ITGAM，ADGRE5与SELL，EXTL1与ADGRE5，EXTL1与EDA2R，PLXDC2与ADGRG2，CNTN5与ITGAM，ITGA2与ITGAM，COMP与ADGRE5，CLEC3B与PLXDC1，CLEC3B与SELL，HMCN2与THBS4，KRT19与AREG，FASLG与EDA2R，THBS4与COMP，CLEC3B与AREG，ADGRE5与PLXDC1，或CEACAM5与AREG。Preferably, the 2markers combination is: TMPRSS15 and GDF15, TMPRSS15 and SPP1, TMPRSS15 and KRT19, SPP1 and ADGRE5, GDF15 and ADGRE5, GDF15 and COMP, SPP1 and COMP, TMPRSS15 and POF1B, PTX3 and THBS4, TMPRSS15 and EDA2R, TMPRSS15 and LMNB2, PTX3 and HMCN2, PTX3 and RET, GDF15 and PTX3, TMPRSS15 and FASLG, TMPRSS15 and ENPP6, COMP and LMNB2, PTX3 and ENPP6, GDF15 and ADGRG2, THBS4 and LMNB2, SPP1 and SOD3, PTX3 and KRT19, GDF15 and PLXDC2, PTX3 and POF1B, TMPRSS15 and SOD3, TMPRSS15 and PTX3, COMP and EDA2R, PLXDC2 and POF1B, GDF15 and ITGA2, GDF15 and HMCN2, TMPRSS15 and CEACAM5, TMPRSS15 and AREG, PTX3 and ADGRG2, GDF15 and THBS4, SPP1 and CLEC3B, TMPRSS15 and FCRL1, RET and SOD3, TMPRSS15 and ITGA11, GDF15 and RET, HMCN2 and SPP1, PTX3 and PLXDC2, GDF15 and PLXDC1, SPP1 and PLXDC1, PTX3 and COMP, PTX3 and FASLG, PTX3 and ITGAM, ITGA11 and LMNB2, PLXDC2 and SPP1, PTX3 and CLEC3B, GDF15 and ITGA11, PLXDC2 and KRT19, TMPRSS15 and THBS4, GDF15 and CLEC3B, TMPRSS15 and ITGAM, ENPP6 and SPP1, PTX3 and ITGA2, SPP1 and ITGA2, GDF15 and ITGAM, PLXDC2 and CEACAM5, COMP and KRT19, PTX3 and SELL, SPP1 and ADGRG2, PTX3 and CNTN5, ITGB7 and POF1B, PLXDC2 and LMNB2, TMPRSS15 and SELL, CEACAM5 and COMP, KRT19 and ITGB7, GDF15 and ITGB7, LMNB2 and SOD3, TMPRSS15 and RET, PTX3 and SPP1, POF1B and SOD3, PTX3 and SOD3, ADGRG2 and LMNB2, TMPRSS15 and EXTL1, GDF15 and FCRL1, PTX3 and FCRL 1, ITGA11 and POF1B, LMNB2 and ITGAM, ITGA11 and KRT19, TMPRSS15 and ITGA2, PTX3 and EXTL1, TMPRSS15 and ITGB7, GDF15 and CNTN5, TMPRSS15 and CLEC3B, PTX3 and ITGA11, TMPRSS15 and HMCN2, PLXDC2 and AREG, TMPRSS15 and COMP, THBS4 and POF1B, POF1B and ITGA2, LMNB2 and ITGB7, TMPRSS15 and ADGRG2, KRT19 and ADGRE5, CEACAM5 and SOD3, TMPRSS15 and PLXDC2, THBS4 and EDA2R, HMCN2 and AREG, HMCN2 and POF1B, FCRL1 and COMP, SPP1 and FCRL1, ENPP6 and ITGA11, C OMP and POF1B, PTX3 and PLXDC1, FCRL1 and LMNB2, LMNB2 and PLXDC1, KRT19 and ITGA2, SPP1 and FASLG, ADGRE5 and EDA2R, CEACAM5 and ITGB7, LMNB2 and ADGRE5, PTX3 and ITGB7, PTX3 and LMNB2, CEACAM5 and ITGA11, POF1B and ADGRE5, FASLG and PLXDC1, KRT19 and EXTL1, KRT19 and FASLG, PLXDC2 and ITGA11, ENPP6 and EXTL1, FCRL1 and SOD3, LMNB2 and CLEC3B, GDF15 and EXTL1, THBS4 and AREG, POF1B and PLXDC1, ENPP6 and THBS4, CEACAM5 and CLEC3B, PTX3 and CEACAM5, RET and FASLG, FCRL1 and POF1B, ENPP6 and POF1B, and FCRL1, ENPP6 and LMNB2, ADGRG2 and KRT19, CEACAM5 and ITGAM, PTX3 and EDA2R, GDF15 and ENPP6, SPP1 and THBS4, PLXDC2 and EDA2R, ENPP6 and ADGRE5, KRT19 and SELL, FASLG and SOD3, KRT19 and SOD3, ENPP6 and KRT19, TMPRSS15 and CNTN5, SPP1 and RET, GDF15 and CEACAM5, HMCN2 and FASLG, ADGRG2 and POF1B, ITGA2 and EDA2R, RET and POF1B, CEACAM5 and THBS4, TMPRSS15 and PLXDC1, COMP and FASLG, RET and LMNB2, CEACAM5 and AD GRE5, ENPP6 and CEACAM5, CLEC3B and EDA2R, ITGA11 and CNTN5, SPP1 and EXTL1, ENPP6 and COMP, ADGRG2 and EDA2R, ITGA11 and SOD3, SPP1 and SELL, GDF15 and SOD3, SPP1 and ITGA11, COMP and AREG, PLXDC2 and FASLG, RET and CLEC3B, RET and KRT19, CEACAM5 and RET, LMNB2 and CNTN5, THBS4 and KRT19, FCRL1 and CLEC3B, LMNB2 and ITGA2, HMCN2 and CLEC3B, SPP1 and ITGB7, POF1B and FASLG, POF1B and EXTL1, KRT19 and PLXDC1, HMCN2 and CEACAM5, ADGRG2 and FASLG, FCRL1 and KRT 19, PLXDC2 and FCRL1, ENPP6 and AREG, LMNB2 and FASLG, HMCN2 and EDA2R, ITGB7 and EDA2R, PTX3 and ADGRE5, HMCN2 and LMNB2, THBS4 and RET, PLXDC2 and RET, CEACAM5 and ADGRG2, PLXDC2 and EXTL1, RET and ITGB7, FCRL1 and ADGRE5, THBS4 and ITGA11, ENPP6 and PLXDC1, ITGA11 and EDA2R, CEACAM5 and FASLG, RET and ITGA2, ENPP6 and FASLG, ITGA11 and FASLG, COMP and SELL, ENPP6 and RET, THBS4 and FASLG, ITGA11 and COMP, ITGA2 and SOD3, ITGA11 and SELL, TMPRSS15 and ADGR E5, THBS4 and CLEC3B, PLXDC2 and ITGB7, ITGA11 and RET, HMCN2 and KRT19, PLXDC1 and EDA2R, CEACAM5 and EXTL1, FCRL1 and THBS4, RET and AREG, FCRL1 and EXTL1, POF1B and ITGAM, ENPP6 and ITGB7, ADGRG2 and AREG, ITGA11 and CLEC3B, PLXDC2 and ITGAM, CLEC3B and EXTL1, LMNB2 and KRT19, CEACAM5 and ITGA2, FCRL1 and ITGA11, SOD3 and AREG, ENPP6 and ITGAM, ITGA2 and AREG, PLXDC2 and ADGRE5, POF1B and CLEC3B, CNTN5 and CLEC3B, ENPP6 and EDA2R, KRT19 and CLEC3B, GD F15 and POF1B, PTX3 and AREG, FASLG and EXTL1, PLXDC2 and COMP, GDF15 and KRT19, SOD3 and EDA2R, ITGAM and SOD3, KRT19 and ITGAM, GDF15 and SELL, PLXDC2 and CNTN5, CNTN5 and AREG, ENPP6 and HMCN2, CNTN5 and FASLG, FCRL1 and ADGRG2, SPP1 and LMNB2, CEACAM5 and PLXDC1, SPP1 and CEACAM5, ADGRG2 and RET, CNTN5 and EDA2R, ADGRG2 and SOD3, ADGRG2 and EXTL1, THBS4 and CNTN5, ITGB7 and AREG, FCRL1 and EDA2R, SPP1 and CNTN5, GDF15 and FASLG, FASLG and ITGA2, ADGRG2 and P LXDC1, FCRL1 and CNTN5, HMCN2 and ITGA11, HMCN2 and FCRL1, FCRL1 and ITGA2, EXTL1 and AREG, ITGA11 and EXTL1, FASLG and CLEC3B, CEACAM5 and CNTN5, ITGB7 and CLEC3B, SPP1 and ITGAM, GDF15 and SPP1, CNTN5 and ADGRE5, FASLG and ITGAM, ADGRG2 and CLEC3B, ITGAM and AREG, FCRL1 and RET, LMNB2 and EXTL1, HMCN2 and PLXDC1, FASLG and AREG, SPP1 and KRT19, ITGA11 and ITGB7, ITGA11 and AREG, RET and EXTL1, POF1B and SELL, PLXDC2 and HMCN2, CNTN5 and PLXDC1, PLXDC2 and THBS4, THBS4 and EXTL1, KRT19 and CNTN5, CEACAM5 and EDA2R, FCRL1 and ITGB7, CEACAM5 and LMNB2, COMP and RET, CNTN5 and POF1B, POF1B and EDA2R, FCRL1 and FASLG, ITGA2 and EXTL1, ITGB7 and PLXDC1, ADGRG2 and COMP, COMP and EXTL1, PLXDC2 and CLEC3B, ENPP6 and SOD3, PLXDC2 and ITGA2, CNTN5 and EXTL1, ITGA11 and PLXDC1, ADGRG2 and CNTN5, ITGAM and EDA2R, SPP1 and POF1B, CLEC3B and ITGA2, ITGB7 and FASLG, ITGA11 and ADGRE5, PLXDC2 and ENPP6, GDF15 and LMNB2, CNTN5 and SOD3, CNTN5 and ITGA2, ITGA11 and ADGRG2, HMCN2 and CNTN5, CEACAM5 and KRT19, RET and ADGRE5, FASLG and ADGRE5, PLXDC2 and SOD3, HMCN2 and SOD3, SOD3 and PLXDC1, EXTL1 and SOD3, CEACAM5 and SELL, HMCN2 and ADGRG2, CEACAM5 and POF1B, COMP and ITGA2, ADGRE5 and AREG, CLEC3B and ITGAM, FCRL1 and CEACAM5, HMCN2 and ITGA2, FCRL1 and PLXDC1, CLEC3B and ADGRE5, ENPP6 and ITGA2, GDF15 and AREG, LMNB2 and POF1B, HMCN2 and ITGAM, ITGB7 and EXTL1, HMCN2 and EXTL1,LMNB2 and SELL,PLXDC2 and PLXDC1,FCRL1 and ITGAM,ENPP6 and CLEC3B,SOD3 and SELL,THBS4 and ITGAM,COMP and ITGB7,CNTN5 and ITGB7,THBS4 and SELL,HMCN2 and COMP,PLXDC1 and SELL,HMCN2 and SELL,COMP and CNTN5,ITGB7 and ITGA2,PLXDC1 and AREG,SPP1 and AREG,HMCN2 and RET,RET and CNTN5,THBS4 and ITGA2,RET and EDA2R,HMCN2 and ITGB7,RET and ITGAM,ADGRG2 and ITGAM,FCRL1 and AREG,THBS4 and ITGB7,THBS4 and SOD3,AREG and SELL,ITGB7 and SOD3,ENPP 6 and CNTN5, COMP and PLXDC1, ITGA2 and SELL, KRT19 and EDA2R, HMCN2 and ADGRE5, ITGA2 and ADGRE5, EXTL1 and ITGAM, THBS4 and PLXDC1, EXTL1 and PLXDC1, GDF15 and EDA2R, KRT19 and POF1B, RET and PLXDC1, THBS4 and ADGRE5, ITGAM and PLXDC1, EXTL1 and SELL, COMP and SOD3, ENPP6 and SELL, ITGA11 and ITGA2, ADGRG2 and ITGA2, ENPP6 and ADGRG2, ADGRG2 and ADGRE5, THBS4 and ADGRG2, ITGA11 and ITGAM, SPP1 and EDA2R, RET and SELL, ADGRG2 and ITGB7, COMP and ITGAM, CLEC 3B and SOD3, ITGB7 and ADGRE5, CNTN5 and SELL, PLXDC2 and SELL, ITGB7 and ITGAM, COMP and CLEC3B, ITGB7 and SELL, ITGA2 and PLXDC1, FCRL1 and SELL, ADGRE5 and SOD3, ADGRE5 and ITGAM, ADGRE5 and SELL, EXTL1 and ADGRE5, EXTL1 and EDA2R, PLXDC2 and ADGRG2, CNTN5 and ITGAM, ITGA2 and ITGAM, COMP and ADGRE5, CLEC3B and PLXDC1, CLEC3B and SELL, HMCN2 and THBS4, KRT19 and AREG, FASLG and EDA2R, THBS4 and COMP, CLEC3B and AREG, ADGRE5 and PLXDC1, or CEACAM5 and AREG.
优选地，所述2markers组合为a1)～a2)中任一种：Preferably, the 2 markers combination is any one of a1) to a2):
a1)D中的任意两种；a1) Any two of D;
a2)所述C中的任意一种，以及D中的任意一种；a2) any one of C and any one of D;
所述D为ADAMTS8、ADGRE1、ADGRE2、AGR3、ANGPTL4、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CFP、CKAP4、CNTN1、CNTN4、CRTAC1、DCC、DLK1、ESM1、FAP、FCER2、FGF21、GCG、GNAS、GRK5、GSN、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGB1、ITIH3、ITM2A、LBP、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PROK1、PTPRS、RBFOX3、SERPINA1、SPON2、TCL1A、TNC、TNFRSF10B、TNFRSF11A、VSIG4(即D与C的并集为B，且D与C无交集)。The D is ADAMTS8, ADGRE1, ADGRE2, AGR3, ANGPTL4, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CFP, CKAP4, CNTN1, CNTN4, CRTAC1, DCC, DLK1, ESM1, FAP, FCER2, FGF21, GCG, GNAS, GRK5, GSN, IFNL1, IGDCC4, IGFBP1, IGSF3, I L4R, IL6, ITGB1, ITIH3, ITM2A, LBP, LPL, MEGF9, MMP12, NOTCH1, NOTCH3, NOS2, NPY, NT5C1A, NTRK2, PCDH7, PGA4, PKD1, PROK1, PTPRS, RBFOX3, SERPINA1, SPON2, TCL1A, TNC, TNFRSF10B, TNFRSF11A, VSIG4 (i.e., the union of D and C is B, and D and C have no intersection).
优选地，所述2markers组合为：TMPRSS15与TNFRSF10B，NOTCH1与GDF15，TMPRSS15与MMP12，TMPRSS15与IL4R，PTX3与CNTN4，GDF15与DLK1，NOTCH3与SPP1，TMPRSS15与PGA4，GDF15与ITGB1，TMPRSS15与CCL7，TNFRSF11A与TMPRSS15，PLXDC2与ESM1，NT5C1A_TMPRSS15，SPP1与NTRK2，COMP与TNFRSF10B，SPP1与PTPRS，CRTAC1与GDF15，CD48与GDF15，SPP1与ITGB1，TMPRSS15与CKAP4，TMPRSS15与LBP，ADGRE2与GDF15，TMPRSS15与IL6，GNAS与TMPRSS15，NOTCH1与SPP1，GDF15与IGSF3，TMPRSS15与RBFOX3，LMNB2与ITGB1，PLXDC2与IGFBP1，GDF15与NTRK2，GDF15与PKD1，PTX3与BMP4，NOTCH3与GDF15，GDF15与CNTN1，TMPRSS15与SPON2，COMP与PGA4，ADGRE5与TNFRSF10B，TMPRSS15与FGF21，TMPRSS15_VSIG4，GDF15与CFP，ADGRE1与GDF15，SPP1与LPL，TMPRSS15与TNC，GDF15与FAP，COMP与RBFOX3，ITGB1与TNFRSF10B，CRTAC1与SPP1，ADGRE2与LMNB2，PTX3与NTRK2，COMP与MMP12，DLK1与EDA2R，TNFRSF11A与COMP，THBS4与MMP12，ADGRG2与ESM1，PTX3与LPL，ITGB7与IL4R，SPP1与PKD1，HMCN2与MMP12，GDF15与C9，TMPRSS15与ITM2A，GSN与PTX3，GDF15与GCG，NOTCH3与PTX3，GDF15与AGR3，NTRK2与ESM1，GDF15与PCDH7，TMPRSS15与ESM1，TNFRSF10B与DLK1，GDF15与MEGF9，THBS4与IL4R，TMPRSS15与GCG，COMP与IL4R，THBS4与TNFRSF10B，TMPRSS15与SERPINA1，SOD3与PGA4，ADGRE2与SPP1，COMP与VSIG4，NTRK2与TNFRSF10B，PLXDC2与GCG，NT5C1A与COMP，NOTCH3与TNFRSF10B，SPP1与BAG3，COMP与CKAP4，ITGB1与EDA2R，TMPRSS15与ASAH2，TMPRSS15与C9，PLXDC2与IL4R，TMPRSS15与BMP4，NOTCH3与LMNB2，CD48与SPP1，NOTCH1与TNFRSF10B，PTX3与GCG，TMPRSS15与TCL1A，TMPRSS15与ADAMTS8，LMNB2与DLK1，TMPRSS15与NOS2，SPP1与CNTN1，SPP1与DLK1，NOTCH1与LMNB2，DCC与TMPRSS15，TMPRSS15与PKD1，GDF15与CNTN4，PTX3与ADAMTS8，NOTCH1与KRT19，ADGRE2与PTX3，PLXDC2与SPON2，PLXDC2与RBFOX3，TMPRSS15与ITIH3，TMPRSS15与NTRK2，TMPRSS15与CFP，THBS4与CKAP4，DCC与PTX3，FASLG与ESM1，PTX3与PTPRS，PTX3与ITGB1，SPP1与CNTN4，TNFRSF10B与PLXDC1，ADGRE2与TNFRSF10B，PTX3与TCL1A，GSN与SPP1，COMP与ESM1，ESM1与CNTN4，PTX3与MMP12，NT5C1A与ITGB1，ADGRE1与LMNB2，GDF15与ADAMTS8，ADGRE1与PTX3，PTX3与CNTN1，PLXDC2与TCL1A，TMPRSS15与CNTN4，CKAP4与DLK1，NOTCH3与KRT19，ADGRG2与SERPINA1，PTX3与ITM2A，CLEC3B与TNFRSF10B，TNFRSF11A与THBS4，POF1B与NPY，NOTCH3与ESM1，GDF15与PROK1，POF1B与PCDH7，ADGRE2与CEACAM5，ADGRE1与KRT19，ENPP6与ESM1，CLEC3B与PGA4，SPP1与ADAMTS8，ITGB7与TNFRSF10B，HMCN2与SERPINA1，ADGRE2与KRT19，PTX3与ASAH2，PTX3与AGR3，ADGRG2与TNFRSF10B，KRT19与GCG，VSIG4与DLK1，TMPRSS15与LPL，LMNB2与CNTN1，TMPRSS15与CDH23，PTX3与PCDH7，SPP1与PROK1，SPP1与FAP，CNTN4与CKAP4，TMPRSS15与GRK5，TMPRSS15与CNTN1，IL4R与SOD3，TMPRSS15与CEACAM16，PTX3与IL4R，HMCN2与IGFBP1，THBS4与SERPINA1，TMPRSS15与FAP，THBS4与ESM1，TMPRSS15与ANGPTL4，TMPRSS15与IGFBP1，IL4R与DLK1，THBS4与PGA4，PLXDC2与TNFRSF10B，GDF15与LPL，TNFRSF10B与CNTN4，GDF15与BAG3，GDF15与TCL1A，ADGRG2与ANGPTL4，CNTN5与ESM1，SPP1与PCDH7，GDF15与NPY，LMNB2与CNTN4，ADGRE5与PGA4，ENPP6与MMP12，NOTCH3与MMP12，COMP与LBP，SPP1与FCER2，THBS4与ANGPTL4，GDF15与FCER2，NTRK2与LMNB2，GNAS与GDF15，NTRK2与PGA4，KRT19与TCL1A，SPP1与GCG，HMCN2与TNFRSF10B，CEACAM5与NTRK2，HMCN2与IL4R，RET与MMP12，ENPP6与ASAH2，TMPRSS15与MEGF9，SPP1与TCL1A，COMP与CCL7，IGDCC4与TMPRSS15，KRT19与NPY，POF1B与ITGB1，GDF15与BMP4，TMPRSS15与PROK1，PTX3与PGA4，TNFRSF11A与DLK1，NOTCH3与EDA2R，CD48与TMPRSS15，PLXDC1与LBP，HMCN2与ESM1，ITGA11与RBFOX3，KRT19与PKD1，NTRK2与EDA2R，ITGB1与PGA4，KRT19与DLK1，IL4R与PTPRS，KRT19与CFP，ENPP6与IGFBP1，SOD3与ESM1，HMCN2与C9，MMP12与PLXDC1，HMCN2与ITIH3，COMP与IL6，SPP1与IGSF3，PTX3与IL6，NOTCH1与PTX3，SPON2与DLK1，TNFRSF10B与NPY，ENPP6与TNFRSF10B，KRT19与PCDH7，ITGB1与MMP12，LMNB2与PTPRS，CD48与TNFRSF10B，ADGRE1与TMPRSS15，GSN与GDF15，PGA4与DLK1，HMCN2与PGA4，PTX3与FCER2，GDF15与PTPRS，NTRK2与POF1B，COMP与TCL1A，ENPP6与BMP4，HMCN2与CFP，GDF15与ASAH2，MMP12与SOD3，IL4R与PLXDC1，POF1B与ADAMTS8，GNAS与PTX3，RET与TNFRSF10B，ADGRG2与IL4R，ADGRE2与RBFOX3，MMP12与NPY，ADGRE1与IL4R，ITGB1与ANGPTL4，NTRK2与IL4R，NTRK2与KRT19，KRT19_ANGPTL4，POF1B与PKD1，NOTCH3与SERPINA1，TMPRSS15与PCDH7，MMP12与ADGRE5，ITGB1与ESM1，CEACAM5与CNTN4，TMPRSS15与IFNL1，TNFRSF10B与BAG3，NT5C1A与DLK1，TMPRSS15与ITGB1，SPP1与CFP，NT5C1A与ADGRE5，IGFBP1与BMP4，ITGA11与IGFBP1，CLEC3B与CKAP4，SERPINA1与CNTN4，MMP12与PTPRS，PTX3与IGSF3，ITGA2与MMP12，KRT19与ITGB1，NOTCH3与POF1B，COMP与ASAH2，POF1B与LPL，PTX3与TNFRSF10B，NT5C1A与THBS4，RET与ANGPTL4，ENPP6与GCG，FCRL1与TNFRSF10B，CEACAM5与GCG，或NOTCH1与POF1B。Preferably, the 2markers combination is: TMPRSS15 and TNFRSF10B, NOTCH1 and GDF15, TMPRSS15 and MMP12, TMPRSS15 and IL4R, PTX3 and CNTN4, GDF15 and DLK1, NOTCH3 and SPP1, TMPRSS15 and PGA4, GDF15 and ITGB1, TMPRSS15 and CCL7, TNFRSF11A and TMPRSS15, PLXDC2 and ESM1, NT5C1A_TMPRSS15, SPP1 and NTRK2, COMP and TNFRSF10B, SP P1 and PTPRS, CRTAC1 and GDF15, CD48 and GDF15, SPP1 and ITGB1, TMPRSS15 and CKAP4, TMPRSS15 and LBP, ADGRE2 and GDF15, TMPRSS15 and IL6, GNAS and TMPRSS15, NOTCH1 and SPP1, GDF15 and IGSF3, TMPRSS15 and RBFOX3, LMNB2 and ITGB1, PLXDC2 and IGFBP1, GDF15 and NTRK2, GDF15 and PKD1, PTX3 and BMP4, NOTCH3 and GDF15, GDF15 with CNTN1, TMPRSS15 with SPON2, COMP with PGA4, ADGRE5 with TNFRSF10B, TMPRSS15 with FGF21, TMPRSS15_VSIG4, GDF15 with CFP, ADGRE1 with GDF15, SPP1 with LPL, TMPRSS15 with TNC, GDF15 with FAP, COMP with RBFOX3, ITGB1 with TNFRSF10B, CRTAC1 with SPP1, ADGRE2 with LMNB2, PTX3 with NTRK2, COMP with MMP12, DLK1 with EDA2R, TNFRSF11 A and COMP, THBS4 and MMP12, ADGRG2 and ESM1, PTX3 and LPL, ITGB7 and IL4R, SPP1 and PKD1, HMCN2 and MMP12, GDF15 and C9, TMPRSS15 and ITM2A, GSN and PTX3, GDF15 and GCG, NOTCH3 and PTX3, GDF15 and AGR3, NTRK2 and ESM1, GDF15 and PCDH7, TMPRSS15 and ESM1, TNFRSF10B and DLK1, GDF15 and MEGF9, THBS4 and IL4R, TMPRSS15 and GCG, CO MP and IL4R, THBS4 and TNFRSF10B, TMPRSS15 and SERPINA1, SOD3 and PGA4, ADGRE2 and SPP1, COMP and VSIG4, NTRK2 and TNFRSF10B, PLXDC2 and GCG, NT5C1A and COMP, NOTCH3 and TNFRSF10B, SPP1 and BAG3, COMP and CKAP4, ITGB1 and EDA2R, TMPRSS15 and ASAH2, TMPRSS15 and C9, PLXDC2 and IL4R, TMPRSS15 and BMP4, NOTCH3 and LMNB 2, CD48 and SPP1, NOTCH1 and TNFRSF10B, PTX3 and GCG, TMPRSS15 and TCL1A, TMPRSS15 and ADAMTS8, LMNB2 and DLK1, TMPRSS15 and NOS2, SPP1 and CNTN1, SPP1 and DLK1, NOTCH1 and LMNB2, DCC and TMPRSS15, TMPRSS15 and PKD1, GDF15 and CNTN4, PTX3 and ADAMTS8, NOTCH1 and KRT19, ADGRE2 and PTX3, PLXDC2 and SPON2, PLXDC2 and RBF OX3, TMPRSS15 and ITIH3, TMPRSS15 and NTRK2, TMPRSS15 and CFP, THBS4 and CKAP4, DCC and PTX3, FASLG and ESM1, PTX3 and PTPRS, PTX3 and ITGB1, SPP1 and CNTN4, TNFRSF10B and PLXDC1, ADGRE2 and TNFRSF10B, PTX3 and TCL1A, GSN and SPP1, COMP and ESM1, ESM1 and CNTN4, PTX3 and MMP12, NT5C1A and ITGB1, ADGRE1 and LMNB2, GDF1 5 and ADAMTS8, ADGRE1 and PTX3, PTX3 and CNTN1, PLXDC2 and TCL1A, TMPRSS15 and CNTN4, CKAP4 and DLK1, NOTCH3 and KRT19, ADGRG2 and SERPINA1, PTX3 and ITM2A, CLEC3B and TNFRSF10B, TNFRSF11A and THBS4, POF1B and NPY, NOTCH3 and ESM1, GDF15 and PROK1, POF1B and PCDH7, ADGRE2 and CEACAM5, ADGRE1 and KRT19, ENPP6 and ESM1 , CLEC3B and PGA4, SPP1 and ADAMTS8, ITGB7 and TNFRSF10B, HMCN2 and SERPINA1, ADGRE2 and KRT19, PTX3 and ASAH2, PTX3 and AGR3, ADGRG2 and TNFRSF10B, KRT19 and GCG, VSIG4 and DLK1, TMPRSS15 and LPL, LMNB2 and CNTN1, TMPRSS15 and CDH23, PTX3 and PCDH7, SPP1 and PROK1, SPP1 and FAP, CNTN4 and CKAP4, TMPRSS15 and GRK5, TM PRSS15 and CNTN1, IL4R and SOD3, TMPRSS15 and CEACAM16, PTX3 and IL4R, HMCN2 and IGFBP1, THBS4 and SERPINA1, TMPRSS15 and FAP, THBS4 and ESM1, TMPRSS15 and ANGPTL4, TMPRSS15 and IGFBP1, IL4R and DLK1, THBS4 and PGA4, PLXDC2 and TNFRSF10B, GDF15 and LPL, TNFRSF10B and CNTN4, GDF15 and BAG3, GDF15 and TCL1A, ADGRG2 with ANGPTL4, CNTN5 with ESM1, SPP1 with PCDH7, GDF15 with NPY, LMNB2 with CNTN4, ADGRE5 with PGA4, ENPP6 with MMP12, NOTCH3 with MMP12, COMP with LBP, SPP1 with FCER2, THBS4 with ANGPTL4, GDF15 with FCER2, NTRK2 with LMNB2, GNAS with GDF15, NTRK2 with PGA4, KRT19 with TCL1A, SPP1 with GCG, HMCN2 with TNFRSF10B, CEACAM5 with NTRK2, HMCN2 with I L4R, RET and MMP12, ENPP6 and ASAH2, TMPRSS15 and MEGF9, SPP1 and TCL1A, COMP and CCL7, IGDCC4 and TMPRSS15, KRT19 and NPY, POF1B and ITGB1, GDF15 and BMP4, TMPRSS15 and PROK1, PTX3 and PGA4, TNFRSF11A and DLK1, NOTCH3 and EDA2R, CD48 and TMPRSS15, PLXDC1 and LBP, HMCN2 and ESM1, ITGA11 and RBFOX3, KRT19 and PKD1, NTRK 2 and EDA2R, ITGB1 and PGA4, KRT19 and DLK1, IL4R and PTPRS, KRT19 and CFP, ENPP6 and IGFBP1, SOD3 and ESM1, HMCN2 and C9, MMP12 and PLXDC1, HMCN2 and ITIH3, COMP and IL6, SPP1 and IGSF3, PTX3 and IL6, NOTCH1 and PTX3, SPON2 and DLK1, TNFRSF10B and NPY, ENPP6 and TNFRSF10B, KRT19 and PCDH7, ITGB1 and MMP12, LMNB2 and PTPRS, CD 48 and TNFRSF10B, ADGRE1 and TMPRSS15, GSN and GDF15, PGA4 and DLK1, HMCN2 and PGA4, PTX3 and FCER2, GDF15 and PTPRS, NTRK2 and POF1B, COMP and TCL1A, ENPP6 and BMP4, HMCN2 and CFP, GDF15 and ASAH2, MMP12 and SOD3, IL4R and PLXDC1, POF1B and ADAMTS8, GNAS and PTX3, RET and TNFRSF10B, ADGRG2 and IL4R, ADGRE2 and RBFOX3, MMP 12 and NPY, ADGRE1 and IL4R, ITGB1 and ANGPTL4, NTRK2 and IL4R, NTRK2 and KRT19, KRT19_ANGPTL4, POF1B and PKD1, NOTCH3 and SERPINA1, TMPRSS15 and PCDH7, MMP12 and ADGRE5, ITGB1 and ESM1, CEACAM5 and CNTN4, TMPRSS15 and IFNL1, TNFRSF10B and BAG3, NT5C1A and DLK1, TMPRSS15 and ITGB1, SPP1 and CFP, NT5C1A and ADGRE 5, IGFBP1 and BMP4, ITGA11 and IGFBP1, CLEC3B and CKAP4, SERPINA1 and CNTN4, MMP12 and PTPRS, PTX3 and IGSF3, ITGA2 and MMP12, KRT19 and ITGB1, NOTCH3 and POF1B, COMP and ASAH2, POF1B and LPL, PTX3 and TNFRSF10B, NT5C1A and THBS4, RET and ANGPTL4, ENPP6 and GCG, FCRL1 and TNFRSF10B, CEACAM5 and GCG, or NOTCH1 and POF1B.
优选地，所述2markers组合为E中的任意2种，所述E为：AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1。Preferably, the 2 markers combination is any 2 of E, and E is: AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1.
优选地，所述2markers组合为：TMPRSS15与GDF15，GDF15与COMP，TMPRSS15与EDA2R，GDF15与PTX3，TMPRSS15与PTX3，COMP与EDA2R，TMPRSS15与CEACAM5，TMPRSS15与AREG，TMPRSS15与FCRL1，PTX3与COMP，CEACAM5与COMP，GDF15与FCRL1，PTX3与FCRL1，TMPRSS15与COMP，FCRL1与COMP，PTX3与CEACAM5，PTX3与EDA2R，GDF15与CEACAM5，COMP与AREG，PTX3与AREG，FCRL1与EDA2R，CEACAM5与EDA2R，FCRL1与CEACAM5，GDF15与AREG，FCRL1与AREG，GDF15与EDA2R，CEACAM5与AREG，NOTCH1与GDF15，TMPRSS15与TNC，TMPRSS15与SERPINA1，NOTCH1与PTX3，NOTCH1与TMPRSS15，PTX3与TNC，COMP与SERPINA1，NOTCH1与CEACAM5，COMP与TNC，FCRL1与SERPINA1，NOTCH1与SERPINA1，CEACAM5与SERPINA1，PTX3与SERPINA1，NOTCH1与AREG，NOTCH1与FCRL1，FCRL1与TNC，CEACAM5与TNC，NOTCH1与TNC，NOTCH1与COMP，AREG与TNC，SERPINA1与TNC，或SERPINA1与AREG。Preferably, the 2markers combination is: TMPRSS15 and GDF15, GDF15 and COMP, TMPRSS15 and EDA2R, GDF15 and PTX3, TMPRSS15 and PTX3, COMP and EDA2R, TMPRSS15 and CEACAM5, TMPRSS15 and AREG, TMPRSS15 and FCRL1, PTX3 and COMP, CEACAM5 and COMP, GDF15 and FCRL1, PTX3 and FCRL1, TMPRSS15 and COMP, FCRL1 and COMP, PTX3 and CEACAM5, PTX3 and EDA2R, GDF15 and CEACAM5, COMP and AREG, PTX3 and AREG, FCRL1 and EDA2R, CEACAM5 and EDA2R, FCRL1 and CEACAM5, GDF15 and F CRL1 with AREG, GDF15 with EDA2R, CEACAM5 with AREG, NOTCH1 with GDF15, TMPRSS15 with TNC, TMPRSS15 with SERPINA1, NOTCH1 with PTX3, NOTCH1 with TMPRSS15, PTX3 with TNC, COMP with SERPINA1, NOTCH1 with CEACAM5, COMP with TNC, FCRL1 with SERPINA1, NOTCH1 with SERPINA1, CEACAM5 with SERPINA1, PTX3 with SERPINA1, NOTCH1 with AREG, NOTCH1 with FCRL1, FCRL1 with TNC, CEACAM5 with TNC, NOTCH1 with TNC, NOTCH1 with COMP, AREG with TNC, SERPINA1 with TNC, or SERPINA1 with AREG.
优选地，所述A包含3markers组合，所述3markers组合为所述B中的任意3种。Preferably, A comprises a combination of 3 markers, and the combination of 3 markers is any 3 of the combinations in B.
优选地，所述3markers组合为：SPP1、COMP与FCRL1，TMPRSS15、SPP1与SOD3，AREG、CEACAM5与PLXDC2，PTX3、GDF15与THBS4，SPP1、FCRL1与SOD3，ADGRE1、TMPRSS15与GDF15，COMP、GDF15与PTX3，PTX3、GDF15与CNTN4，TMPRSS15、SPP1与COMP，GDF15、NOTCH1与PTX3，AREG、CEACAM5与DCC，CRTAC1、TMPRSS15与GDF15，CRTAC1、TMPRSS15与SPP1，PTX3、HMCN2与POF1B，GNAS、TMPRSS15与GDF15，TMPRSS15、SPP1与THBS4，AREG、CEACAM5与RET，COMP、FCRL1与GDF15，AREG、CEACAM5与NT5C1A，GDF15、TMPRSS15与TNC，SPP1、ENPP6与ADGRE5，SPP1、ENPP6与COMP，PTX3、POF1B与THBS4，TMPRSS15、COMP与TNFRSF10B，SPP1、PLXDC2与COMP，PTX3、ENPP6与THBS4，NOTCH3、GDF15与PTX3，TMPRSS15、THBS4与TNFRSF10B，ADGRE2、GDF15与PTX3，GDF15、PTX3与TMPRSS15，SPP1、RET与SOD3，TMPRSS15、SOD3与MMP12，ADGRE2、SOD3与SPP1，GNAS、TMPRSS15与RBFOX3，GDF15、COMP与DLK1，SPP1、SOD3与ADGRE5，ADGRE1、TMPRSS15与KRT19，GNAS、NT5C1A与TMPRSS15，CEACAM5、COMP与GDF15，PTX3、GDF15与ADGRG2，PTX3、HMCN2与CNTN4，PTX3、SPP1与COMP，GDF15、EXTL1与DLK1，TMPRSS15、PTX3与KRT19，TMPRSS15、THBS4与MMP12，ADGRE2、DLK1与GDF15，ADGRE1、TMPRSS15与LMNB2，PTX3、PLXDC2与POF1B，AREG、CEACAM5与SELL，NOTCH3、TMPRSS15与SPP1，PTX3、POF1B与CNTN4，PTX3、GDF15与HMCN2，PTX3、GDF15与ADGRE5，TMPRSS15、GDF15与THBS4，ADGRE1、KRT19与LMNB2，ADGRE1、ITGA11与LMNB2，ADGRE1、TMPRSS15与MMP12，AREG、CEACAM5与TNFRSF10B，FCRL1、GDF15与TMPRSS15，TMPRSS15、GDF15与RET，TMPRSS15、KRT19与LMNB2，NOTCH1、SOD3与SPP1，NOTCH1、GDF15与SPP1，TMPRSS15、PTX3与MMP12，SPP1、COMP与LMNB2，TMPRSS15、SPP1与FCRL1，PTX3、GDF15与ITGB1，PTX3、POF1B与SOD3，AREG、CEACAM5与FCER2，CRTAC1、TMPRSS15与TNFRSF10B，TMPRSS15、COMP与MMP12，TMPRSS15、FASLG与MMP12，COMP、GDF15与NOTCH1，TMPRSS15、SPP1与MMP12，PTX3、KRT19与THBS4，COMP、EDA2R与FCRL1，COMP、GDF15与TMPRSS15，ADGRE1、GDF15与PTX3，ADGRE1、TMPRSS15与TNFRSF10B，AREG、CEACAM5与ADAMTS8，NT5C1A、COMP与SPP1，PTX3、RET与SOD3，GDF15、PLXDC2与DLK1，PTX3、GDF15与PLXDC2，TMPRSS15、TNFRSF10B与IL4R，COMP、LMNB2与FCRL1，SPP1、COMP与ITGB1，SPP1、PLXDC2与SOD3，TMPRSS15、GDF15与KRT19，TMPRSS15、SPP1与ENPP6，TMPRSS15、GDF15与PLXDC2，SPP1、COMP与ADGRE5，TMPRSS15、ENPP6与TNFRSF10B，SPP1、COMP与CEACAM5，TMPRSS15、FASLG与TNFRSF10B，SPP1、COMP与FASLG，NOTCH3、PLXDC1与SPP1，ADGRE1、TMPRSS15与IL4R，TMPRSS15、THBS4与LMNB2，AREG、CEACAM5与PROK1，TMPRSS15、SPP1与KRT19，CEACAM5、GDF15与TMPRSS15，COMP、EDA2R与TMPRSS15，ADGRE2、TMPRSS15与GDF15，TMPRSS15、KRT19与FASLG，NOTCH1、ESM1与GDF15，NOTCH3、SPP1与TCL1A，GDF15、COMP与ADGRE5，GDF15、ADGRG2与ADGRE5，SPP1、FASLG与SOD3，SPP1、FCRL1与ADGRE5，GDF15、SPP1与COMP，TMPRSS15、GDF15与TNFRSF10B，GDF15、SPP1与ADGRE5，TNFRSF11A、TMPRSS15与GDF15，PTX3、COMP与POF1B，EDA2R、GDF15与TMPRSS15，TMPRSS15、CLEC3B与MMP12，PTX3、LMNB2与CNTN4，ADGRE1、COMP与GDF15，TMPRSS15、SPP1与CLEC3B，TMPRSS15、GDF15与ITGB7，SPP1、HMCN2与SOD3，AREG、CEACAM5与THBS4，SPP1、ADGRG2与SOD3，GDF15、COMP与ADGRG2，TMPRSS15、GDF15与EXTL1，TMPRSS15、MMP12与IL4R，NOTCH1、LMNB2与SPP1，TMPRSS15、PTX3与SPP1，TMPRSS15、KRT19与TNFRSF10B，NOTCH3、POF1B与PTX3，SPP1、COMP与POF1B，TMPRSS15、GDF15与POF1B，TMPRSS15、GDF15与MMP12，NOTCH3、LMNB2与SPP1，GDF15、ADGRG2与DLK1，TMPRSS15、GDF15与DLK1，TMPRSS15、FCRL1与TNFRSF10B，PTX3、THBS4与FASLG，PTX3、POF1B与RET，TMPRSS15、COMP与IL4R，NOTCH3、PLXDC2与SPP1，TMPRSS15、CLEC3B与TNFRSF10B，TMPRSS15、PTX3与POF1B，TMPRSS15、SPP1与FASLG，GDF15、NOTCH1与TMPRSS15，SPP1、THBS4与ADGRE5，SPP1、COMP与ADGRG2，PTX3、RET与CNTN4，TMPRSS15、SOD3与TNFRSF10B，SPP1、ITGA11与SOD3，SPP1、COMP与CLEC3B，TMPRSS15、LMNB2与MMP12，GDF15、CEACAM5与ADGRE5，GDF15、PLXDC2与COMP，GDF15、FCRL1与ADGRE5，TMPRSS15、GDF15与LMNB2，ADGRE1、POF1B与PTX3，PTX3、POF1B与ADGRG2，SPP1、CLEC3B与ADGRE5，TMPRSS15、SPP1与TNFRSF10B，SPP1、COMP与DLK1，ADGRE1、TMPRSS15与SPP1，ADGRE2、CEACAM5与GDF15，TMPRSS15、GDF15与ENPP6，PTX3、THBS4与IL4R，GDF15、THBS4与DLK1，SPP1、COMP与TNFRSF10B，PTX3、SPP1与THBS4，SPP1、CEACAM5与ADGRE5，GDF15、HMCN2与DLK1，GNAS、TMPRSS15与MMP12，ADGRE1、ADGRG2与GDF15，DCC、CNTN4与PTX3，PTX3、PLXDC2与KRT19，TMPRSS15、SPP1与ADGRE5，TMPRSS15、SPP1与ITGA11，CRTAC1、SPP1与TCL1A，CRTAC1、ADGRE5与GDF15，COMP、GDF15与SERPINA1，NOTCH1、EXTL1与GDF15，COMP、FCRL1与TNFRSF10B，PTX3、GDF15与RET，ADGRE2、CRTAC1与GDF15，GDF15、COMP与LMNB2，PTX3、CEACAM5与CNTN4，GDF15、THBS4与ADGRE5，SPP1、LMNB2与ADGRE5，PTX3、POF1B与ITGA2，TMPRSS15、RET与MMP12，TMPRSS15、SOD3与IL4R，NOTCH3、FCRL1与SPP1，TMPRSS15、ENPP6与MMP12，SPP1、COMP与SOD3，ADGRE2、CLEC3B与SPP1，TMPRSS15、GDF15与ITGA2，NT5C1A、ADGRE5与SPP1，COMP、GDF15与TNC，NOTCH3、SPP1与PTX3，PTX3、SPP1与SOD3，CEACAM5、GDF15与NOTCH1，PTX3、ENPP6与POF1B，ADGRE2、COMP与GDF15，TMPRSS15、POF1B与MMP12，PTX3、THBS4与CNTN4，TMPRSS15、SPP1与PLXDC2，TMPRSS15、PTX3与THBS4，TMPRSS15、LMNB2与SOD3，COMP、EDA2R与PTX3，TMPRSS15、GDF15与HMCN2，GDF15、NOTCH1与SERPINA1TMPRSS15、RET与TNFRSF10B，GNAS、TMPRSS15与IL4RGDF15、LMNB2与DLK1，GDF15、COMP与RET，SPP1、ADGRG2与ADGRE5，NOTCH1、GDF15与THBS4，LMNB2、RET与SOD3，ADGRE1、KRT19与PTX3，GNAS、TNFRSF11A与TMPRSS15，SPP1、PLXDC2与ADGRE5，TMPRSS15、PTX3与FASLG，DCC、COMP与SPP1，PTX3、KRT19与COMP，EDA2R、PTX3与TMPRSS15，TMPRSS15、ITGA11与MMP12，GDF15、ITGA2与DLK1，COMP、POF1B与LMNB2，NOTCH3、TMPRSS15与GDF15，TMPRSS15、SPP1与CEACAM5，TMPRSS15、ITGA11与TNFRSF10B，PTX3、PLXDC2与THBS4，ADGRE2、ENPP6与SPP1，NT5C1A、THBS4与PTX3，TMPRSS15、SPP1与ITGA2，TMPRSS15、ITGB1与TNFRSF10B，CRTAC1、GDF15与PTX3，CEACAM5、RET与SOD3，NOTCH1、LPL与SPP1，TMPRSS15、POF1B与FASLG，TMPRSS15、GDF15与ADGRG2，NOTCH3、TMPRSS15与TNFRSF10B，TMPRSS15、FASLG与IL4R，TMPRSS15、COMP与LMNB2，TMPRSS15、KRT19与ENPP6，GDF15、COMP与HMCN2，TMPRSS15、GDF15与ITGB1，TMPRSS15、ITGB7与MMP12，NOTCH1、AGR3与GDF15，PTX3、EXTL1与CNTN4，NOTCH1、GDF15与KRT19，NT5C1A、TMPRSS15与COMP，SPP1、THBS4与CLEC3B，TMPRSS15、FCRL1与MMP12，NOTCH3、ESM1与PLXDC2，TMPRSS15、ITGB7与TNFRSF10B，TNFRSF11A、TMPRSS15与MMP12，SPP1、COMP与ITGA2，PTX3、THBS4与EXTL1，TMPRSS15、PLXDC2与IL4R，TMPRSS15、SPP1与EXTL1，PTX3、ITGA11与POF1B，GDF15、RET与DLK1，AREG、COMP与GDF15，TMPRSS15、PTX3与IL4R，NOTCH1、FAP与GDF15，PTX3、THBS4与LMNB2，NOTCH3、NT5C1A与SPP1，PTX3、COMP与TNFRSF10B，PLXDC2、ITGA11与LMNB2，GNAS、TMPRSS15与LMNB2，GNAS、TMPRSS15与SPP1，GNAS、TMPRSS15与AREG，PTX3、KRT19与FASLG，PTX3、SPP1与HMCN2，ADGRE1、GDF15与ITGA2，PTX3、COMP与IL4R，PTX3、SPP1与CNTN4，PTX3、POF1B与EXTL1，TMPRSS15、PTX3与TNFRSF10B，TMPRSS15、GDF15与ITGA11，PTX3、TNFRSF10B与CNTN4，TMPRSS15、SPP1与ADGRG2，CD48、TMPRSS15与GDF15，TMPRSS15、GDF15与FASLG，ADGRE1、DLK1与GDF15，TMPRSS15、SPP1与RET，NOTCH1、CEACAM5与SPP1，CRTAC1、TMPRSS15与EDA2R，GDF15、COMP与ITGA11，GDF15、COMP与CLEC3B，PTX3、GDF15与DLK1，ADGRE2、CLEC3B与GDF15，COMP、RET与TNFRSF10B，PTX3、POF1B与ITGB7，TNFRSF11A、THBS4与PTX3，CEACAM5、COMP与EDA2R，NOTCH1、SERPINA1与SPP1，SPP1、KRT19与ADGRE5，ADGRE1、COMP与LMNB2，GNAS、TMPRSS15与TNFRSF10B，CEACAM5、PTX3与TMPRSS15，ADGRE2、POF1B与PTX3，NOTCH1、DLK1与GDF15，SPP1、SOD3与EXTL1，PLXDC2、COMP与LMNB2，COMP、POF1B与FCRL1，SPP1、PLXDC2与THBS4，GSN、TMPRSS15与PGA4，GDF15、THBS4与CLEC3B，PLXDC2、KRT19与LMNB2，TMPRSS15、LMNB2与FCRL1，TMPRSS15、ITGA2与MMP12，ADGRE1、COMP与TNFRSF10B，TMPRSS15、TNFRSF10B与DLK1，SPP1、COMP与IL4R，RET、SOD3与TNFRSF10B，GNAS、TMPRSS15与POF1B，THBS4、LMNB2与CLEC3B，GDF15、CLEC3B与ADGRE5，EDA2R、TMPRSS15与TNC，TNFRSF11A、COMP与GDF15，ADGRE1、CLEC3B与GDF15，GDF15、COMP与ITGB1，PTX3、KRT19与ENPP6，SPP1、COMP与HMCN2，TMPRSS15、SPP1与HMCN2，TMPRSS15、GDF15与SPP1，TMPRSS15、PLXDC2与LMNB2，PTX3、KRT19与EXTL1，SPP1、ITGA11与ADGRE5，GDF15、KRT19与COMP，EDA2R、FCRL1与TMPRSS15，TNFRSF11A、TMPRSS15与PGA4，AREG、CEACAM5与RBFOX3，DCC、COMP与GDF15，LMNB2、FCRL1与SOD3，TMPRSS15、POF1B与TNFRSF10B，CD48、GDF15与PTX3，PTX3、GDF15与CLEC3B，PTX3、POF1B与FASLG，PTX3、THBS4与MMP12，NOTCH1、PROK1与SPP1，COMP、EDA2R与GDF15，NOTCH1、TMPRSS15与TNFRSF10B，PTX3、SPP1与ADGRG2，TNFRSF11A、ADGRE5与SPP1，PTX3、GDF15与EXTL1，ADGRE2、GDF15与TCL1A，GNAS、ADGRE5与GDF15，PTX3、ENPP6与ITGA11，NOTCH1、COMP与SPP1，NT5C1A、TMPRSS15与THBS4，ADGRE2、CRTAC1与SPP1，TMPRSS15、THBS4与IL4R，TMPRSS15、GDF15与ADGRE5，NT5C1A、TMPRSS15与PTX3，ADGRE2、COMP与SPP1，TMPRSS15、GDF15与SOD3，NOTCH1、GDF15与POF1B，TMPRSS15、LMNB2与CNTN4，SPP1、KRT19与COMP，TMPRSS15、SPP1与LMNB2，CD48、COMP与GDF15，TMPRSS15、ITGA11与LMNB2，SPP1、CEACAM5与SOD3，ADGRE2、TNFRSF11A与GDF15，SPP1、SOD3与ITGA2，ITGA11、LMNB2与SOD3，AREG、EDA2R与TMPRSS15，NOTCH1、GDF15与LMNB2，ADGRE2、GNAS与GDF15，NOTCH1、EXTL1与SPP1，TMPRSS15、HMCN2与TNFRSF10B，PTX3、THBS4与FCRL1，TMPRSS15、ITGA2与TNFRSF10B，NOTCH1、GDF15与ITGA11，PTX3、SPP1与CLEC3B，PTX3、THBS4与RET，TNFRSF11A、TMPRSS15与THBS4，NOTCH1、SPP1与TNFRSF10B，NOTCH1、TMPRSS15与SPP1，ADGRE1、GDF15与PKD1，GDF15、LMNB2与ADGRE5，ADGRE2、GDF15与THBS4，GDF15、ADGRE5与DLK1，CD48、CLEC3B与SPP1，NOTCH1、SPP1与PTX3，GDF15、SERPINA1与TMPRSS15，TMPRSS15、ITGA11与IL4R，GNAS、TMPRSS15与CCL7，TNFRSF11A、BAG3与PLXDC2，SPP1、POF1B与ADGRE5，ADGRE2、ESM1与GDF15，GSN、SPP1与THBS4，ADGRE2、GDF15与HMCN2，DCC、THBS4与PTX3，TMPRSS15、ENPP6与LMNB2，PTX3、KRT19与SOD3，TMPRSS15、ADGRG2与MMP12，PTX3、IL4R与CNTN4，SPP1、FCRL1与CLEC3B，TMPRSS15、MMP12与TNFRSF10B，ADGRE1、LMNB2与THBS4，PTX3、PLXDC2与IL4R，TMPRSS15、GDF15与CNTN4，GDF15、ITGB1与DLK1，ADGRE1、GDF15与ITGA11，TMPRSS15、SPP1与ITGB1，TMPRSS15、KRT19与MMP12，TMPRSS15、KRT19与IL4R，SPP1、THBS4与FCRL1，SPP1、COMP与MMP12，TMPRSS15、KRT19与SOD3，PTX3、SOD3与IL4R，FCRL1、GDF15与PTX3，NOTCH3、CLEC3B与SPP1，GNAS、TMPRSS15与KRT19，TMPRSS15、KRT19与COMP，TMPRSS15、CEACAM5与MMP12，GSN、TMPRSS15与TNFRSF10B，NOTCH1、IGFBP1与SPP1，TMPRSS15、LMNB2与FASLG，SPP1、COMP与CNTN4，TMPRSS15、PTX3与ENPP6，TMPRSS15、GDF15与IL4R，TMPRSS15、SPP1与DLK1，ADGRE1、ITGA2与LMNB2，ADGRE2、ADGRG2与GDF15，NT5C1A、TMPRSS15与KRT19，GSN、GDF15与PTX3，NOTCH3、ADGRE5与SPP1，ADGRE1、CNTN5与LMNB2，ADGRE1、CRTAC1与GDF15，COMP、FCRL1与MMP12，SPP1、SOD3与ITGB1，ADGRE2、LMNB2与SPP1，PTX3、HMCN2与IL4R，PTX3、COMP与LMNB2，NOTCH3、TMPRSS15与MMP12，GNAS、TMPRSS15与PGA4，NOTCH1、C9与GDF15，ADGRE1、PLXDC1与SPP1，SPP1、RET与ADGRE5，PTX3、KRT19与RET，NOTCH3、ESM1与MMP12，NOTCH3、ENPP6与SPP1，GDF15、COMP与POF1B，ADGRE1、GDF15与HMCN2，ADGRE1、LMNB2与SOD3，PTX3、SOD3与CNTN4，GDF15、COMP与THBS4，GDF15、HMCN2与ADGRE5，TNFRSF11A、TMPRSS15与TNFRSF10B，CRTAC1、GDF15与SPP1，NT5C1A、CNTN4与PTX3，COMP、CEACAM5与LMNB2，NOTCH1、GDF15与PROK1，GDF15、PLXDC2与ADGRE5，NOTCH1、POF1B与PTX3，ADGRE1、TNFRSF11A与TMPRSS15，SPP1、TNFRSF10B与ADGRE5，PTX3、KRT19与ADGRG2，GDF15、COMP与ITGB7，TMPRSS15、EXTL1与IL4R，SPP1、COMP与EXTL1，ADGRE1、GDF15与THBS4，CEACAM5、EDA2R与TMPRSS15，ADGRE1、TMPRSS15与POF1B，SPP1、COMP与THBS4，PTX3、THBS4与ADGRG2，GSN、ADGRE5与SPP1，ADGRE1、ADGRG2与LMNB2，ADGRE2、TMPRSS15与SPP1，SPP1、HMCN2与CLEC3B，SPP1、COMP与ITGA11，AREG、GDF15与TMPRSS15，SPP1、COMP与RET，GNAS、LMNB2与PLXDC2，PTX3、GDF15与ITGA2，SPP1、ENPP6与SOD3，NOTCH3、CEACAM5与SPP1，GDF15、HMCN2与ITGB1，TMPRSS15、PLXDC2与MMP12，NOTCH3、ADGRG2与SPP1，TMPRSS15、KRT19与EXTL1，PTX3、KRT19与CNTN4，SPP1、ADGRG2与ITGA2，GNAS、TMPRSS15与LBP，NOTCH1、GDF15与HMCN2，CRTAC1、NOTCH1与GDF15，NOTCH3、COMP与GDF15，NOTCH3、PROK1与SPP1，TMPRSS15、SPP1与IL4R，GDF15、HMCN2与CLEC3B，GNAS、COMP与GDF15，TMPRSS15、MMP12与DLK1，TMPRSS15、KRT19与CEACAM5，ADGRE2、FCRL1与GDF15，GNAS、NOTCH1与GDF15，CEACAM5、COMP与PTX3，GDF15、LMNB2与ITGB1，ADGRE2、TMPRSS15与TNFRSF10B，TMPRSS15、PTX3与RET，CD48、TMPRSS15与TNFRSF10B，PTX3、THBS4与ITGA2，SPP1、LMNB2与ITGB1，ADGRE1、TMPRSS15与PGA4，TMPRSS15、PTX3与CNTN4，TMPRSS15、COMP与POF1B，SPP1、ADGRG2与CLEC3B，PTX3、HMCN2与CLEC3B，SPP1、HMCN2与ADGRE5，POF1B、FCRL1与SOD3，GSN、THBS4与PTX3，COMP、LMNB2与TNFRSF10B，TMPRSS15、KRT19与FCRL1，TMPRSS15、DLK1与IL4R，NOTCH3、KRT19与PTX3，GDF15、COMP与TNFRSF10B，TMPRSS15、SPP1与ITGB7，COMP、CEACAM5与TNFRSF10B，TMPRSS15、ENPP6与IL4R，TMPRSS15、TNFRSF10B与CNTN4，PTX3、HMCN2与FASLG，PTX3、ITGA11与CNTN4，PTX3、THBS4与TNFRSF10B，PTX3、POF1B与FCRL1，GDF15、ENPP6与DLK1，ITGA11、POF1B与SOD3，NT5C1A、TMPRSS15与SPP1，SPP1、ENPP6与THBS4，PTX3、GDF15与POF1B，NOTCH3、ITM2A与PTX3，GDF15、POF1B与ADGRE5，ADGRE1、COMP与SPP1，TNFRSF11A、ADGRE5与GDF15，CRTAC1、ADGRE5与SPP1，PLXDC2、LMNB2与FCRL1，NOTCH3、TNFRSF10B与PTX3，PTX3、GDF15与SOD3，PTX3、FASLG与CNTN4，PTX3、GDF15与ITGA11，PTX3、PLXDC2与FASLG，GDF15、THBS4与ITGB1，PTX3、FASLG与ADGRG2，PLXDC2、SOD3与IL4R，PTX3、KRT19与ADGRE5，LMNB2、ADGRG2与SOD3，GNAS、TMPRSS15与EDA2R，SPP1、ADGRE5与IL4R，NOTCH1、TMPRSS15与MMP12，GNAS、TMPRSS15与FASLG，GSN、TMPRSS15与SPP1，ITGA11、RET与SOD3，DCC、CLEC3B与PTX3，PTX3、ITGA11与THBS4，PTX3、COMP与MMP12，ADGRE2、GDF15与LPL，CRTAC1、GDF15与TCL1A，NOTCH3、ESM1与TNFRSF10B，GSN、CNTN4与PTX3，TMPRSS15、SPP1与CNTN4，GDF15、COMP与ITGA2，PTX3、ADGRG2与IL4R，ADGRE1、ENPP6与LMNB2，SPP1、PLXDC2与HMCN2，NOTCH1、CLEC3B与SPP1，SPP1、ENPP6与DLK1，RET、SOD3与IL4R，TNFRSF11A、CNTN4与PTX3，NOTCH1、PLXDC1与SPP1，SPP1、PLXDC2与ITGA2，SPP1、PLXDC2与DLK1，GDF15、COMP与CNTN4，ADGRE1、NOTCH1与GDF15，TMPRSS15、PLXDC2与KRT19，TMPRSS15、POF1B与IL4R，TMPRSS15、POF1B与THBS4，NOTCH3、PGA4与PTX3，TNFRSF11A、TMPRSS15与FASLG，TMPRSS15、PLXDC2与TNFRSF10B，GDF15、ITGA11与ADGRE5，SPP1、CLEC3B与ITGA2，NT5C1A、TMPRSS15与FAP，NOTCH3、TMPRSS15与KRT19，GSN、TMPRSS15与EDA2R，TMPRSS15、POF1B与SOD3，SPP1、THBS4与SOD3，NOTCH1、CNTN5与GDF15，GDF15、KRT19与ADGRE5，PTX3、ENPP6与FASLG，NOTCH3、COMP与SPP1，GNAS、TMPRSS15与ENPP6，NOTCH3、LPL与SPP1，GDF15、FCRL1与DLK1，NOTCH3、SOD3与SPP1，TMPRSS15、KRT19与THBS4，ADGRE1、ITGA2与SPP1，COMP、LMNB2与ADGRG2，GSN、FASLG与PTX3，ADGRE2、LMNB2与SOD3，NOTCH3、ITGA2与SPP1，TMPRSS15、PTX3与ADGRG2，CRTAC1、HMCN2与SPP1，TMPRSS15、TNFRSF10B与ADGRE5，GDF15、COMP与MMP12，SPP1、FASLG与ADGRE5，TMPRSS15、POF1B与EXTL1，PTX3、ENPP6与CNTN4，PTX3、KRT19与FCRL1，PTX3、POF1B与ITGB1，ADGRE2、PTPRS与SPP1，PTX3、KRT19与HMCN2，CD48、SOD3与SPP1，NOTCH1、KRT19与SPP1，GDF15、COMP与FASLG，LMNB2、SOD3与DLK1，ADGRE1、HMCN2与PTX3，PTX3、THBS4与CLEC3B，或FCRL1、GDF15与NOTCH1；即上述622个3markers组合中的任意一种。Preferably, the 3 markers combination is: SPP1, COMP and FCRL1, TMPRSS15, SPP1 and SOD3, AREG, CEACAM5 and PLXDC2, PTX3, GDF15 and THBS4, SPP1, FCRL1 and SOD3, ADGRE1, TMPRSS15 and GDF15, COMP, GDF15 and PTX3, PTX3, GDF15 and CNTN4, TMPRSS15, SPP1 and COMP, GDF15 , NOTCH1 and PTX3, AREG, CEACAM5 and DCC, CRTAC1, TMPRSS15 and GDF15, CRTAC1, TMPRSS15 and SPP1, PTX3, HMCN2 and POF1B, GNAS, TMPRSS15 and GDF15, TMPRSS15, SPP1 and THBS4, AREG, CEACAM5 and RET, COMP, FCRL1 and GDF15, AREG, CEACAM5 and NT5C1A, G DF15, TMPRSS15 and TNC, SPP1, ENPP6 and ADGRE5, SPP1, ENPP6 and COMP, PTX3, POF1B and THBS4, TMPRSS15, COMP and TNFRSF10B, SPP1, PLXDC2 and COMP, PTX3, ENPP6 and THBS4, NOTCH3, GDF15 and PTX3, TMPRSS15, THBS4 and TNFRSF10B, ADGRE2, GDF15 and PT X3, GDF15, PTX3 and TMPRSS15, SPP1, RET and SOD3, TMPRSS15, SOD3 and MMP12, ADGRE2, SOD3 and SPP1, GNAS, TMPRSS15 and RBFOX3, GDF15, COMP and DLK1, SPP1, SOD3 and ADGRE5, ADGRE1, TMPRSS15 and KRT19, GNAS, NT5C1A and TMPRSS15, CEACAM5, COMP and GD F15, PTX3, GDF15 and ADGRG2, PTX3, HMCN2 and CNTN4, PTX3, SPP1 and COMP, GDF15, EXTL1 and DLK1, TMPRSS15, PTX3 and KRT19, TMPRSS15, THBS4 and MMP12, ADGRE2, DLK1 and GDF15, ADGRE1, TMPRSS15 and LMNB2, PTX3, PLXDC2 and POF1B, AREG, CEACAM5 and SE LL, NOTCH3, TMPRSS15 and SPP1, PTX3, POF1B and CNTN4, PTX3, GDF15 and HMCN2, PTX3, GDF15 and ADGRE5, TMPRSS15, GDF15 and THBS4, ADGRE1, KRT19 and LMNB2, ADGRE1, ITGA11 and LMNB2, ADGRE1, TMPRSS15 and MMP12, AREG, CEACAM5 and TNFRSF10B, FCRL1 , GDF15 and TMPRSS15, TMPRSS15, GDF15 and RET, TMPRSS15, KRT19 and LMNB2, NOTCH1, SOD3 and SPP1, NOTCH1, GDF15 and SPP1, TMPRSS15, PTX3 and MMP12, SPP1, COMP and LMNB2, TMPRSS15, SPP1 and FCRL1, PTX3, GDF15 and ITGB1, PTX3, POF1B and SOD3, AREG, CEACAM5 and FCER2, CRTAC1, TMPRSS15 and TNFRSF10B, TMPRSS15, COMP and MMP12, TMPRSS15, FASLG and MMP12, COMP, GDF15 and NOTCH1, TMPRSS15, SPP1 and MMP12, PTX3, KRT19 and THBS4, COMP, EDA2R and FCRL1, COMP, GDF15 and TMPRSS15, ADGRE1, GDF15 and PTX3, ADGRE1, TMPRSS15 and TNFRSF10B, AREG, CEACAM5 and ADAMTS8, NT5C1A, COMP and SPP1, PTX3, RET and SOD3, GDF15, PLXDC2 and DLK1, PTX3, GDF15 and PLXDC2, TMPRSS15, TNFRSF10B and IL4R, COMP, LMNB2 and FCRL1, SPP1, COMP and ITGB1, SPP1, PLXD C2 and SOD3, TMPRSS15, GDF15 and KRT19, TMPRSS15, SPP1 and ENPP6, TMPRSS15, GDF15 and PLXDC2, SPP1, COMP and ADGRE5, TMPRSS15, ENPP6 and TNFRSF10B, SPP1, COMP and CEACAM5, TMPRSS15, FASLG and TNFRSF10B, SPP1, COMP and FASLG, NOTCH3, PLXDC1 with SPP1, ADGRE1, TMPRSS15 and IL4R, TMPRSS15, THBS4 and LMNB2, AREG, CEACAM5 and PROK1, TMPRSS15, SPP1 and KRT19, CEACAM5, GDF15 and TMPRSS15, COMP, EDA2R and TMPRSS15, ADGRE2, TMPRSS15 and GDF15, TMPRSS15, KRT19 and FASLG, NOTCH1, ESM1 and GDF15, NOTCH3, SPP1 and TCL1A, GDF15, COMP and ADGRE5, GDF15, ADGRG2 and ADGRE5, SPP1, FASLG and SOD3, SPP1, FCRL1 and ADGRE5, GDF15, SPP1 and COMP, TMPRSS15, GDF15 and TNFRSF10B, GDF15, SPP1 and ADGRE5, TNFRSF11A, TMPRSS15 and GDF15, PTX3, C OMP and POF1B, EDA2R, GDF15 and TMPRSS15, TMPRSS15, CLEC3B and MMP12, PTX3, LMNB2 and CNTN4, ADGRE1, COMP and GDF15, TMPRSS15, SPP1 and CLEC3B, TMPRSS15, GDF15 and ITGB7, SPP1, HMCN2 and SOD3, AREG, CEACAM5 and THBS4, SPP1, ADGRG2 and SOD3, GDF 15, COMP and ADGRG2, TMPRSS15, GDF15 and EXTL1, TMPRSS15, MMP12 and IL4R, NOTCH1, LMNB2 and SPP1, TMPRSS15, PTX3 and SPP1, TMPRSS15, KRT19 and TNFRSF10B, NOTCH3, POF1B and PTX3, SPP1, COMP and POF1B, TMPRSS15, GDF15 and POF1B, TMPRSS15, GDF1 5 and MMP12, NOTCH3, LMNB2 and SPP1, GDF15, ADGRG2 and DLK1, TMPRSS15, GDF15 and DLK1, TMPRSS15, FCRL1 and TNFRSF10B, PTX3, THBS4 and FASLG, PTX3, POF1B and RET, TMPRSS15, COMP and IL4R, NOTCH3, PLXDC2 and SPP1, TMPRSS15, CLEC3B and TNFRSF10B, TMPRSS15, PTX3 and POF1B, TMPRSS15, SPP1 and FASLG, GDF15, NOTCH1 and TMPRSS15, SPP1, THBS4 and ADGRE5, SPP1, COMP and ADGRG2, PTX3, RET and CNTN4, TMPRSS15, SOD3 and TNFRSF10B, SPP1, ITGA11 and SOD3, SPP1, COMP and CLEC3B, TMPRSS15, LMNB2 and M MP12, GDF15, CEACAM5 and ADGRE5, GDF15, PLXDC2 and COMP, GDF15, FCRL1 and ADGRE5, TMPRSS15, GDF15 and LMNB2, ADGRE1, POF1B and PTX3, PTX3, POF1B and ADGRG2, SPP1, CLEC3B and ADGRE5, TMPRSS15, SPP1 and TNFRSF10B, SPP1, COMP and DLK1, ADGRE1, TMPRSS15 and SPP1, ADGRE2, CEACAM5 and GDF15, TMPRSS15, GDF15 and ENPP6, PTX3, THBS4 and IL4R, GDF15, THBS4 and DLK1, SPP1, COMP and TNFRSF10B, PTX3, SPP1 and THBS4, SPP1, CEACAM5 and ADGRE5, GDF15, HMCN2 and DLK1, GNAS, TMPRSS15 and MMP12, ADG RE1, ADGRG2 and GDF15, DCC, CNTN4 and PTX3, PTX3, PLXDC2 and KRT19, TMPRSS15, SPP1 and ADGRE5, TMPRSS15, SPP1 and ITGA11, CRTAC1, SPP1 and TCL1A, CRTAC1, ADGRE5 and GDF15, COMP, GDF15 and SERPINA1, NOTCH1, EXTL1 and GDF15, COMP, FCRL1 and TNFRS F10B, PTX3, GDF15 and RET, ADGRE2, CRTAC1 and GDF15, GDF15, COMP and LMNB2, PTX3, CEACAM5 and CNTN4, GDF15, THBS4 and ADGRE5, SPP1, LMNB2 and ADGRE5, PTX3, POF1B and ITGA2, TMPRSS15, RET and MMP12, TMPRSS15, SOD3 and IL4R, NOTCH3, FCRL1 and SPP1, TMPRSS15, ENPP6 and MMP12, SPP1, COMP and SOD3, ADGRE2, CLEC3B and SPP1, TMPRSS15, GDF15 and ITGA2, NT5C1A, ADGRE5 and SPP1, COMP, GDF15 and TNC, NOTCH3, SPP1 and PTX3, PTX3, SPP1 and SOD3, CEACAM5, GDF15 and NOTCH1, PTX3, ENPP6 and POF1B, ADGRE 2. COMP and GDF15, TMPRSS15, POF1B and MMP12, PTX3, THBS4 and CNTN4, TMPRSS15, SPP1 and PLXDC2, TMPRSS15, PTX3 and THBS4, TMPRSS15, LMNB2 and SOD3, COMP, EDA2R and PTX3, TMPRSS15, GDF15 and HMCN2, GDF15, NOTCH1 and SERPINA1TMPRSS15, RET and TNF RSF10B, GNAS, TMPRSS15 and IL4RGDF15, LMNB2 and DLK1, GDF15, COMP and RET, SPP1, ADGRG2 and ADGRE5, NOTCH1, GDF15 and THBS4, LMNB2, RET and SOD3, ADGRE1, KRT19 and PTX3, GNAS, TNFRSF11A and TMPRSS15, SPP1, PLXDC2 and ADGRE5, TMPRSS15 and PTX3 FASLG, DCC, COMP and SPP1, PTX3, KRT19 and COMP, EDA2R, PTX3 and TMPRSS15, TMPRSS15, ITGA11 and MMP12, GDF15, ITGA2 and DLK1, COMP, POF1B and LMNB2, NOTCH3, TMPRSS15 and GDF15, TMPRSS15, SPP1 and CEACAM5, TMPRSS15, ITGA11 and TNFRSF10B, PTX3 , PLXDC2 and THBS4, ADGRE2, ENPP6 and SPP1, NT5C1A, THBS4 and PTX3, TMPRSS15, SPP1 and ITGA2, TMPRSS15, ITGB1 and TNFRSF10B, CRTAC1, GDF15 and PTX3, CEACAM5, RET and SOD3, NOTCH1, LPL and SPP1, TMPRSS15, POF1B and FASLG, TMPRSS15, GDF15 and ADG RG2, NOTCH3, TMPRSS15 and TNFRSF10B, TMPRSS15, FASLG and IL4R, TMPRSS15, COMP and LMNB2, TMPRSS15, KRT19 and ENPP6, GDF15, COMP and HMCN2, TMPRSS15, GDF15 and ITGB1, TMPRSS15, ITGB7 and MMP12, NOTCH1, AGR3 and GDF15, PTX3, EXTL1 and CNTN4, NOTCH1, GDF15 and KRT19, NT5C1A, TMPRSS15 and COMP, SPP1, THBS4 and CLEC3B, TMPRSS15, FCRL1 and MMP12, NOTCH3, ESM1 and PLXDC2, TMPRSS15, ITGB7 and TNFRSF10B, TNFRSF11A, TMPRSS15 and MMP12, SPP1, COMP and ITGA2, PTX3, THBS4 and EXTL1, TMPR SS15, PLXDC2 and IL4R, TMPRSS15, SPP1 and EXTL1, PTX3, ITGA11 and POF1B, GDF15, RET and DLK1, AREG, COMP and GDF15, TMPRSS15, PTX3 and IL4R, NOTCH1, FAP and GDF15, PTX3, THBS4 and LMNB2, NOTCH3, NT5C1A and SPP1, PTX3, COMP and TNFRSF10B, PLXDC2, I TGA11 and LMNB2, GNAS, TMPRSS15 and LMNB2, GNAS, TMPRSS15 and SPP1, GNAS, TMPRSS15 and AREG, PTX3, KRT19 and FASLG, PTX3, SPP1 and HMCN2, ADGRE1, GDF15 and ITGA2, PTX3, COMP and IL4R, PTX3, SPP1 and CNTN4, PTX3, POF1B and EXTL1, TMPRSS15, PTX3 and T NFRSF10B, TMPRSS15, GDF15 and ITGA11, PTX3, TNFRSF10B and CNTN4, TMPRSS15, SPP1 and ADGRG2, CD48, TMPRSS15 and GDF15, TMPRSS15, GDF15 and FASLG, ADGRE1, DLK1 and GDF15, TMPRSS15, SPP1 and RET, NOTCH1, CEACAM5 and SPP1, CRTAC1, TMPRSS15 and EDA2R, GDF15, COMP and ITGA11, GDF15, COMP and CLEC3B, PTX3, GDF15 and DLK1, ADGRE2, CLEC3B and GDF15, COMP, RET and TNFRSF10B, PTX3, POF1B and ITGB7, TNFRSF11A, THBS4 and PTX3, CEACAM5, COMP and EDA2R, NOTCH1, SERPINA1 and SPP1, SPP1, KRT19 with ADGRE5, ADGRE1, COMP and LMNB2, GNAS, TMPRSS15 and TNFRSF10B, CEACAM5, PTX3 and TMPRSS15, ADGRE2, POF1B and PTX3, NOTCH1, DLK1 and GDF15, SPP1, SOD3 and EXTL1, PLXDC2, COMP and LMNB2, COMP, POF1B and FCRL1, SPP1, PLXDC2 and THBS4, GSN, TMPRS S15 and PGA4, GDF15, THBS4 and CLEC3B, PLXDC2, KRT19 and LMNB2, TMPRSS15, LMNB2 and FCRL1, TMPRSS15, ITGA2 and MMP12, ADGRE1, COMP and TNFRSF10B, TMPRSS15, TNFRSF10B and DLK1, SPP1, COMP and IL4R, RET, SOD3 and TNFRSF10B, GNAS, TMPRSS15 and PO F1B, THBS4, LMNB2 and CLEC3B, GDF15, CLEC3B and ADGRE5, EDA2R, TMPRSS15 and TNC, TNFRSF11A, COMP and GDF15, ADGRE1, CLEC3B and GDF15, GDF15, COMP and ITGB1, PTX3, KRT19 and ENPP6, SPP1, COMP and HMCN2, TMPRSS15, SPP1 and HMCN2, TMPRSS15, GDF 15 and SPP1, TMPRSS15, PLXDC2 and LMNB2, PTX3, KRT19 and EXTL1, SPP1, ITGA11 and ADGRE5, GDF15, KRT19 and COMP, EDA2R, FCRL1 and TMPRSS15, TNFRSF11A, TMPRSS15 and PGA4, AREG, CEACAM5 and RBFOX3, DCC, COMP and GDF15, LMNB2, FCRL1 and SOD3, TMPRS S15, POF1B and TNFRSF10B, CD48, GDF15 and PTX3, PTX3, GDF15 and CLEC3B, PTX3, POF1B and FASLG, PTX3, THBS4 and MMP12, NOTCH1, PROK1 and SPP1, COMP, EDA2R and GDF15, NOTCH1, TMPRSS15 and TNFRSF10B, PTX3, SPP1 and ADGRG2, TNFRSF11A, ADGRE5 and SPP 1, PTX3, GDF15 and EXTL1, ADGRE2, GDF15 and TCL1A, GNAS, ADGRE5 and GDF15, PTX3, ENPP6 and ITGA11, NOTCH1, COMP and SPP1, NT5C1A, TMPRSS15 and THBS4, ADGRE2, CRTAC1 and SPP1, TMPRSS15, THBS4 and IL4R, TMPRSS15, GDF15 and ADGRE5, NT5C1A, TMPR SS15 and PTX3, ADGRE2, COMP and SPP1, TMPRSS15, GDF15 and SOD3, NOTCH1, GDF15 and POF1B, TMPRSS15, LMNB2 and CNTN4, SPP1, KRT19 and COMP, TMPRSS15, SPP1 and LMNB2, CD48, COMP and GDF15, TMPRSS15, ITGA11 and LMNB2, SPP1, CEACAM5 and SOD3, ADGRE2, TNFRSF11A and GDF15, SPP1, SOD3 and ITGA2, ITGA11, LMNB2 and SOD3, AREG, EDA2R and TMPRSS15, NOTCH1, GDF15 and LMNB2, ADGRE2, GNAS and GDF15, NOTCH1, EXTL1 and SPP1, TMPRSS15, HMCN2 and TNFRSF10B, PTX3, THBS4 and FCRL1, TMPRSS15, ITGA2 and TNF RSF10B, NOTCH1, GDF15 and ITGA11, PTX3, SPP1 and CLEC3B, PTX3, THBS4 and RET, TNFRSF11A, TMPRSS15 and THBS4, NOTCH1, SPP1 and TNFRSF10B, NOTCH1, TMPRSS15 and SPP1, ADGRE1, GDF15 and PKD1, GDF15, LMNB2 and ADGRE5, ADGRE2, GDF15 and THBS4, GDF 15, ADGRE5 and DLK1, CD48, CLEC3B and SPP1, NOTCH1, SPP1 and PTX3, GDF15, SERPINA1 and TMPRSS15, TMPRSS15, ITGA11 and IL4R, GNAS, TMPRSS15 and CCL7, TNFRSF11A, BAG3 and PLXDC2, SPP1, POF1B and ADGRE5, ADGRE2, ESM1 and GDF15, GSN, SPP1 and THBS4 , ADGRE2, GDF15 and HMCN2, DCC, THBS4 and PTX3, TMPRSS15, ENPP6 and LMNB2, PTX3, KRT19 and SOD3, TMPRSS15, ADGRG2 and MMP12, PTX3, IL4R and CNTN4, SPP1, FCRL1 and CLEC3B, TMPRSS15, MMP12 and TNFRSF10B, ADGRE1, LMNB2 and THBS4, PTX3, PLXDC2 and I L4R, TMPRSS15, GDF15 and CNTN4, GDF15, ITGB1 and DLK1, ADGRE1, GDF15 and ITGA11, TMPRSS15, SPP1 and ITGB1, TMPRSS15, KRT19 and MMP12, TMPRSS15, KRT19 and IL4R, SPP1, THBS4 and FCRL1, SPP1, COMP and MMP12, TMPRSS15, KRT19 and SOD3, PTX3, SOD3 with IL4R, FCRL1, GDF15 and PTX3, NOTCH3, CLEC3B and SPP1, GNAS, TMPRSS15 and KRT19, TMPRSS15, KRT19 and COMP, TMPRSS15, CEACAM5 and MMP12, GSN, TMPRSS15 and TNFRSF10B, NOTCH1, IGFBP1 and SPP1, TMPRSS15, LMNB2 and FASLG, SPP1, COMP and CNTN4, TM PRSS15, PTX3 and ENPP6, TMPRSS15, GDF15 and IL4R, TMPRSS15, SPP1 and DLK1, ADGRE1, ITGA2 and LMNB2, ADGRE2, ADGRG2 and GDF15, NT5C1A, TMPRSS15 and KRT19, GSN, GDF15 and PTX3, NOTCH3, ADGRE5 and SPP1, ADGRE1, CNTN5 and LMNB2, ADGRE1, CRTAC1 and GDF15, COMP, FCRL1 and MMP12, SPP1, SOD3 and ITGB1, ADGRE2, LMNB2 and SPP1, PTX3, HMCN2 and IL4R, PTX3, COMP and LMNB2, NOTCH3, TMPRSS15 and MMP12, GNAS, TMPRSS15 and PGA4, NOTCH1, C9 and GDF15, ADGRE1, PLXDC1 and SPP1, SPP1, RET and ADGRE5, PTX3, KRT19 and RET, NOTCH3, ESM1 and MMP12, NOTCH3, ENPP6 and SPP1, GDF15, COMP and POF1B, ADGRE1, GDF15 and HMCN2, ADGRE1, LMNB2 and SOD3, PTX3, SOD3 and CNTN4, GDF15, COMP and THBS4, GDF15, HMCN2 and ADGRE5, TNFRSF11A, TMPRSS15 and TNFRSF10B, CRTA C1, GDF15 and SPP1, NT5C1A, CNTN4 and PTX3, COMP, CEACAM5 and LMNB2, NOTCH1, GDF15 and PROK1, GDF15, PLXDC2 and ADGRE5, NOTCH1, POF1B and PTX3, ADGRE1, TNFRSF11A and TMPRSS15, SPP1, TNFRSF10B and ADGRE5, PTX3, KRT19 and ADGRG2, GDF15, COMP and I TGB7, TMPRSS15, EXTL1 and IL4R, SPP1, COMP and EXTL1, ADGRE1, GDF15 and THBS4, CEACAM5, EDA2R and TMPRSS15, ADGRE1, TMPRSS15 and POF1B, SPP1, COMP and THBS4, PTX3, THBS4 and ADGRG2, GSN, ADGRE5 and SPP1, ADGRE1, ADGRG2 and LMNB2, ADGRE2, TMP RSS15 and SPP1, SPP1, HMCN2 and CLEC3B, SPP1, COMP and ITGA11, AREG, GDF15 and TMPRSS15, SPP1, COMP and RET, GNAS, LMNB2 and PLXDC2, PTX3, GDF15 and ITGA2, SPP1, ENPP6 and SOD3, NOTCH3, CEACAM5 and SPP1, GDF15, HMCN2 and ITGB1, TMPRSS15, PLXDC2 and MMP12, NOTCH3, ADGRG2 and SPP1, TMPRSS15, KRT19 and EXTL1, PTX3, KRT19 and CNTN4, SPP1, ADGRG2 and ITGA2, GNAS, TMPRSS15 and LBP, NOTCH1, GDF15 and HMCN2, CRTAC1, NOTCH1 and GDF15, NOTCH3, COMP and GDF15, NOTCH3, PROK1 and SPP1, TMPRSS15, SP P1 and IL4R, GDF15, HMCN2 and CLEC3B, GNAS, COMP and GDF15, TMPRSS15, MMP12 and DLK1, TMPRSS15, KRT19 and CEACAM5, ADGRE2, FCRL1 and GDF15, GNAS, NOTCH1 and GDF15, CEACAM5, COMP and PTX3, GDF15, LMNB2 and ITGB1, ADGRE2, TMPRSS15 and TNFRSF10B, T MPRSS15, PTX3 and RET, CD48, TMPRSS15 and TNFRSF10B, PTX3, THBS4 and ITGA2, SPP1, LMNB2 and ITGB1, ADGRE1, TMPRSS15 and PGA4, TMPRSS15, PTX3 and CNTN4, TMPRSS15, COMP and POF1B, SPP1, ADGRG2 and CLEC3B, PTX3, HMCN2 and CLEC3B, SPP1, HMCN2 and A DGRE5, POF1B, FCRL1 and SOD3, GSN, THBS4 and PTX3, COMP, LMNB2 and TNFRSF10B, TMPRSS15, KRT19 and FCRL1, TMPRSS15, DLK1 and IL4R, NOTCH3, KRT19 and PTX3, GDF15, COMP and TNFRSF10B, TMPRSS15, SPP1 and ITGB7, COMP, CEACAM5 and TNFRSF10B, TMPRS S15, ENPP6 and IL4R, TMPRSS15, TNFRSF10B and CNTN4, PTX3, HMCN2 and FASLG, PTX3, ITGA11 and CNTN4, PTX3, THBS4 and TNFRSF10B, PTX3, POF1B and FCRL1, GDF15, ENPP6 and DLK1, ITGA11, POF1B and SOD3, NT5C1A, TMPRSS15 and SPP1, SPP1, ENPP6 and THBS4 , PTX3, GDF15 and POF1B, NOTCH3, ITM2A and PTX3, GDF15, POF1B and ADGRE5, ADGRE1, COMP and SPP1, TNFRSF11A, ADGRE5 and GDF15, CRTAC1, ADGRE5 and SPP1, PLXDC2, LMNB2 and FCRL1, NOTCH3, TNFRSF10B and PTX3, PTX3, GDF15 and SOD3, PTX3, FASLG and CNTN 4, PTX3, GDF15 and ITGA11, PTX3, PLXDC2 and FASLG, GDF15, THBS4 and ITGB1, PTX3, FASLG and ADGRG2, PLXDC2, SOD3 and IL4R, PTX3, KRT19 and ADGRE5, LMNB2, ADGRG2 and SOD3, GNAS, TMPRSS15 and EDA2R, SPP1, ADGRE5 and IL4R, NOTCH1, TMPRSS15 and MMP12 , GNAS, TMPRSS15 and FASLG, GSN, TMPRSS15 and SPP1, ITGA11, RET and SOD3, DCC, CLEC3B and PTX3, PTX3, ITGA11 and THBS4, PTX3, COMP and MMP12, ADGRE2, GDF15 and LPL, CRTAC1, GDF15 and TCL1A, NOTCH3, ESM1 and TNFRSF10B, GSN, CNTN4 and PTX3, TMPRSS15 , SPP1 and CNTN4, GDF15, COMP and ITGA2, PTX3, ADGRG2 and IL4R, ADGRE1, ENPP6 and LMNB2, SPP1, PLXDC2 and HMCN2, NOTCH1, CLEC3B and SPP1, SPP1, ENPP6 and DLK1, RET, SOD3 and IL4R, TNFRSF11A, CNTN4 and PTX3, NOTCH1, PLXDC1 and SPP1, SPP1, PLXDC2 and I TGA2, SPP1, PLXDC2 and DLK1, GDF15, COMP and CNTN4, ADGRE1, NOTCH1 and GDF15, TMPRSS15, PLXDC2 and KRT19, TMPRSS15, POF1B and IL4R, TMPRSS15, POF1B and THBS4, NOTCH3, PGA4 and PTX3, TNFRSF11A, TMPRSS15 and FASLG, TMPRSS15, PLXDC2 and TNFRSF 10B, GDF15, ITGA11 and ADGRE5, SPP1, CLEC3B and ITGA2, NT5C1A, TMPRSS15 and FAP, NOTCH3, TMPRSS15 and KRT19, GSN, TMPRSS15 and EDA2R, TMPRSS15, POF1B and SOD3, SPP1, THBS4 and SOD3, NOTCH1, CNTN5 and GDF15, GDF15, KRT19 and ADGRE5, PTX3, ENP P6 and FASLG, NOTCH3, COMP and SPP1, GNAS, TMPRSS15 and ENPP6, NOTCH3, LPL and SPP1, GDF15, FCRL1 and DLK1, NOTCH3, SOD3 and SPP1, TMPRSS15, KRT19 and THBS4, ADGRE1, ITGA2 and SPP1, COMP, LMNB2 and ADGRG2, GSN, FASLG and PTX3, ADGRE2, LMNB2 and SOD3, NOTCH3, ITGA2 and SPP1, TMPRSS15, PTX3 and ADGRG2, CRTAC1, HMCN2 and SPP1, TMPRSS15, TNFRSF10B and ADGRE5, GDF15, COMP and MMP12, SPP1, FASLG and ADGRE5, TMPRSS15, POF1B and EXTL1, PTX3, ENPP6 and CNTN4, PTX3, KRT19 and FCRL1, PTX3, POF1B and I TGB1, ADGRE2, PTPRS and SPP1, PTX3, KRT19 and HMCN2, CD48, SOD3 and SPP1, NOTCH1, KRT19 and SPP1, GDF15, COMP and FASLG, LMNB2, SOD3 and DLK1, ADGRE1, HMCN2 and PTX3, PTX3, THBS4 and CLEC3B, or FCRL1, GDF15 and NOTCH1; that is, any one of the above 622 3markers combinations.
优选地，所述3markers组合为所述E中的任意3种。Preferably, the 3 markers combination is any 3 of the E.
优选地，所述3markers组合为：COMP、GDF15与PTX3，GDF15、NOTCH1与PTX3，COMP、FCRL1与GDF15，GDF15、TMPRSS15与TNC，GDF15、PTX3与TMPRSS15，CEACAM5、COMP与GDF15，FCRL1、GDF15与TMPRSS15，COMP、GDF15与NOTCH1，COMP、EDA2R与FCRL1，COMP、GDF15与TMPRSS15，CEACAM5、GDF15与TMPRSS15，COMP、EDA2R与TMPRSS15，EDA2R、GDF15与TMPRSS15，GDF15、NOTCH1与TMPRSS15，COMP、GDF15与SERPINA1，COMP、GDF15与TNC，CEACAM5、GDF15与NOTCH1，COMP、EDA2R与PTX3，GDF15、NOTCH1与SERPINA1，EDA2R、PTX3与TMPRSS15，AREG、COMP与GDF15，CEACAM5、COMP与EDA2R，CEACAM5、PTX3与TMPRSS15，EDA2R、TMPRSS15与TNC，EDA2R、FCRL1与TMPRSS15，COMP、EDA2R与GDF15，AREG、EDA2R与TMPRSS15，GDF15、SERPINA1与TMPRSS15，FCRL1、GDF15与PTX3，CEACAM5、EDA2R与TMPRSS15，AREG、GDF15与TMPRSS15，CEACAM5、COMP与PTX3，FCRL1、GDF15与NOTCH1，GDF15、NOTCH1与TNC，CEACAM5、COMP与TMPRSS15，CEACAM5、TMPRSS15与TNC，AREG、CEACAM5与TMPRSS15，AREG、COMP与TMPRSS15，PTX3、TMPRSS15与TNC，EDA2R、SERPINA1与TMPRSS15，COMP、PTX3与TMPRSS15，AREG、PTX3与TMPRSS15，AREG、GDF15与NOTCH1，COMP、FCRL1与TMPRSS15，FCRL1、PTX3与TMPRSS15，AREG、COMP与EDA2R，COMP、EDA2R与SERPINA1，COMP、FCRL1与PTX3，CEACAM5、COMP与SERPINA1，CEACAM5、NOTCH1与PTX3，AREG、FCRL1与TMPRSS15，CEACAM5、COMP与TNC，EDA2R、GDF15与NOTCH1，AREG、TMPRSS15与TNC，EDA2R、NOTCH1与TMPRSS15，GDF15、PTX3与TNC，CEACAM5、SERPINA1与TMPRSS15，FCRL1、TMPRSS15与TNC，CEACAM5、COMP与FCRL1，COMP、TMPRSS15与TNC，COMP、PTX3与TNC，CEACAM5、GDF15与PTX3，CEACAM5、FCRL1与TMPRSS15，FCRL1、SERPINA1与TMPRSS15，EDA2R、FCRL1与PTX3，AREG、NOTCH1与TMPRSS15，PTX3、SERPINA1与TMPRSS15，AREG、COMP与PTX3，COMP、SERPINA1与TMPRSS15，CEACAM5、NOTCH1与SERPINA1，COMP、EDA2R与TNC，EDA2R、NOTCH1与PTX3，CEACAM5、NOTCH1与TMPRSS15，AREG、SERPINA1与TMPRSS15，NOTCH1、PTX3与TMPRSS15，COMP、FCRL1与SERPINA1，CEACAM5、FCRL1与PTX3，COMP、NOTCH1与PTX3，AREG、CEACAM5与COMP，EDA2R、GDF15与PTX3，COMP、FCRL1与TNC，AREG、COMP与FCRL1，CEACAM5、EDA2R与NOTCH1，NOTCH1、SERPINA1与TMPRSS15，CEACAM5、FCRL1与GDF15，CEACAM5、EDA2R与PTX3，FCRL1、NOTCH1与TMPRSS15，COMP、EDA2R与NOTCH1，EDA2R、NOTCH1与SERPINA1，AREG、NOTCH1与PTX3，FCRL1、NOTCH1与PTX3，GDF15、PTX3与SERPINA1，COMP、PTX3与SERPINA1，AREG、GDF15与PTX3，FCRL1、GDF15与TNC，FCRL1、GDF15与SERPINA1，NOTCH1、PTX3与SERPINA1，SERPINA1、TMPRSS15与TNC，CEACAM5、COMP与NOTCH1，AREG、FCRL1与PTX3，NOTCH1、PTX3与TNC，FCRL1、PTX3与TNC，CEACAM5、PTX3与TNC，AREG、EDA2R与NOTCH1，CEACAM5、NOTCH1与TNC，EDA2R、FCRL1与NOTCH1，CEACAM5、GDF15与TNC，FCRL1、NOTCH1与SERPINA1，AREG、COMP与TNC，AREG、COMP与SERPINA1，CEACAM5、FCRL1与NOTCH1，AREG、CEACAM5与NOTCH1，AREG、FCRL1与GDF15，CEACAM5、EDA2R与GDF15，CEACAM5、FCRL1与SERPINA1，COMP、FCRL1与NOTCH1，AREG、CEACAM5与PTX3，CEACAM5、GDF15与SERPINA1，AREG、EDA2R与PTX3，NOTCH1、TMPRSS15与TNC，CEACAM5、EDA2R与FCRL1，COMP、NOTCH1与SERPINA1，FCRL1、PTX3与SERPINA1，EDA2R、PTX3与TNC，EDA2R、FCRL1与GDF15，AREG、CEACAM5与GDF15，AREG、COMP与NOTCH1，CEACAM5、PTX3与SERPINA1，EDA2R、PTX3与SERPINA1，COMP、SERPINA1与TNC，NOTCH1、SERPINA1与TNC，COMP、NOTCH1与TMPRSS15，EDA2R、FCRL1与SERPINA1，AREG、EDA2R与FCRL1，AREG、FCRL1与NOTCH1，EDA2R、NOTCH1与TNC，COMP、NOTCH1与TNC，AREG、PTX3与TNC，GDF15、SERPINA1与TNC，AREG、NOTCH1与SERPINA1，CEACAM5、EDA2R与SERPINA1，PTX3、SERPINA1与TNC，CEACAM5、FCRL1与TNC，EDA2R、FCRL1与TNC，AREG、NOTCH1与TNC，FCRL1、NOTCH1与TNC，AREG、EDA2R与GDF15，AREG、GDF15与TNC，CEACAM5、SERPINA1与TNC，AREG、FCRL1与TNC，AREG、CEACAM5与EDA2R，AREG、CEACAM5与FCRL1，CEACAM5、EDA2R与TNC，EDA2R、GDF15与SERPINA1，AREG、PTX3与SERPINA1，EDA2R、GDF15与TNC，FCRL1、SERPINA1与TNC，AREG、FCRL1与SERPINA1，AREG、GDF15与SERPINA1，AREG、CEACAM5与SERPINA1，AREG、CEACAM5与TNC，AREG、EDA2R与SERPINA1，EDA2R、SERPINA1与TNC，AREG、EDA2R与TNC，或AREG、SERPINA1与TNC。Preferably, the 3 markers combination is: COMP, GDF15 and PTX3, GDF15, NOTCH1 and PTX3, COMP, FCRL1 and GDF15, GDF15, TMPRSS15 and TNC, GDF15, PTX3 and TMPRSS15, CEACAM5, COMP and GDF15, FCRL1, GDF15 and TMPRSS15, COMP, GDF15 and NOTCH1, COMP, EDA2R and FCRL1, COMP, GDF15 and TMPR SS15, CEACAM5, GDF15 and TMPRSS15, COMP, EDA2R and TMPRSS15, EDA2R, GDF15 and TMPRSS15, GDF15, NOTCH1 and TMPRSS15, COMP, GDF15 and SERPINA1, COMP, GDF15 and TNC, CEACAM5, GDF15 and NOTCH1, COMP, EDA2R and PTX3, GDF15, NOTCH1 and SERPINA1, EDA2R, PTX3 and TM PRSS15, AREG, COMP and GDF15, CEACAM5, COMP and EDA2R, CEACAM5, PTX3 and TMPRSS15, EDA2R, TMPRSS15 and TNC, EDA2R, FCRL1 and TMPRSS15, COMP, EDA2R and GDF15, AREG, EDA2R and TMPRSS15, GDF15, SERPINA1 and TMPRSS15, FCRL1, GDF15 and PTX3, CEACAM5, EDA2R and TM PRSS15, AREG, GDF15 and TMPRSS15, CEACAM5, COMP and PTX3, FCRL1, GDF15 and NOTCH1, GDF15, NOTCH1 and TNC, CEACAM5, COMP and TMPRSS15, CEACAM5, TMPRSS15 and TNC, AREG, CEACAM5 and TMPRSS15, AREG, COMP and TMPRSS15, PTX3, TMPRSS15 and TNC, EDA2R, SERPINA1 and TMPRSS15, COMP, PTX3 and TMPRSS15, AREG, PTX3 and TMPRSS15, AREG, GDF15 and NOTCH1, COMP, FCRL1 and TMPRSS15, FCRL1, PTX3 and TMPRSS15, AREG, COMP and EDA2R, COMP, EDA2R and SERPINA1, COMP, FCRL1 and PTX3, CEACAM5, COMP and SERPINA1, CEACAM5, NOTCH1 and PTX3 , AREG, FCRL1 and TMPRSS15, CEACAM5, COMP and TNC, EDA2R, GDF15 and NOTCH1, AREG, TMPRSS15 and TNC, EDA2R, NOTCH1 and TMPRSS15, GDF15, PTX3 and TNC, CEACAM5, SERPINA1 and TMPRSS15, FCRL1, TMPRSS15 and TNC, CEACAM5, COMP and FCRL1, COMP, TMPRSS15 and TNC, COMP , PTX3 and TNC, CEACAM5, GDF15 and PTX3, CEACAM5, FCRL1 and TMPRSS15, FCRL1, SERPINA1 and TMPRSS15, EDA2R, FCRL1 and PTX3, AREG, NOTCH1 and TMPRSS15, PTX3, SERPINA1 and TMPRSS15, AREG, COMP and PTX3, COMP, SERPINA1 and TMPRSS15, CEACAM5, NOTCH1 and SERPINA1 , COMP, EDA2R and TNC, EDA2R, NOTCH1 and PTX3, CEACAM5, NOTCH1 and TMPRSS15, AREG, SERPINA1 and TMPRSS15, NOTCH1, PTX3 and TMPRSS15, COMP, FCRL1 and SERPINA1, CEACAM5, FCRL1 and PTX3, COMP, NOTCH1 and PTX3, AREG, CEACAM5 and COMP, EDA2R, GDF15 and PTX3, COMP, FCRL1 and TNC, AREG, COMP and FCRL1, CEACAM5, EDA2R and NOTCH1, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, FCRL1 and GDF15, CEACAM5, EDA2R and PTX3, FCRL1, NOTCH1 and TMPRSS15, COMP, EDA2R and NOTCH1, EDA2R, NOTCH1 and SERPINA1, AREG, NOTCH1 and PTX3, FCRL1, NO TCH1 and PTX3, GDF15, PTX3 and SERPINA1, COMP, PTX3 and SERPINA1, AREG, GDF15 and PTX3, FCRL1, GDF15 and TNC, FCRL1, GDF15 and SERPINA1, NOTCH1, PTX3 and SERPINA1, SERPINA1, TMPRSS15 and TNC, CEACAM5, COMP and NOTCH1, AREG, FCRL1 and PTX3, NOTCH1, PTX3 and TNC, F CRL1, PTX3 and TNC, CEACAM5, PTX3 and TNC, AREG, EDA2R and NOTCH1, CEACAM5, NOTCH1 and TNC, EDA2R, FCRL1 and NOTCH1, CEACAM5, GDF15 and TNC, FCRL1, NOTCH1 and SERPINA1, AREG, COMP and TNC, AREG, COMP and SERPINA1, CEACAM5, FCRL1 and NOTCH1, AREG, CEACAM5 and NOTC H1, AREG, FCRL1 and GDF15, CEACAM5, EDA2R and GDF15, CEACAM5, FCRL1 and SERPINA1, COMP, FCRL1 and NOTCH1, AREG, CEACAM5 and PTX3, CEACAM5, GDF15 and SERPINA1, AREG, EDA2R and PTX3, NOTCH1, TMPRSS15 and TNC, CEACAM5, EDA2R and FCRL1, COMP, NOTCH1 and SERPINA1 , FCRL1, PTX3 and SERPINA1, EDA2R, PTX3 and TNC, EDA2R, FCRL1 and GDF15, AREG, CEACAM5 and GDF15, AREG, COMP and NOTCH1, CEACAM5, PTX3 and SERPINA1, EDA2R, PTX3 and SERPINA1, COMP, SERPINA1 and TNC, NOTCH1, SERPINA1 and TNC, COMP, NOTCH1 and TMPRSS15, EDA2R, F CRL1 and SERPINA1, AREG, EDA2R and FCRL1, AREG, FCRL1 and NOTCH1, EDA2R, NOTCH1 and TNC, COMP, NOTCH1 and TNC, AREG, PTX3 and TNC, GDF15, SERPINA1 and TNC, AREG, NOTCH1 and SERPINA1, CEACAM5, EDA2R and SERPINA1, PTX3, SERPINA1 and TNC, CEACAM5, FCRL1 and TNC, EDA 2R, FCRL1 and TNC, AREG, NOTCH1 and TNC, FCRL1, NOTCH1 and TNC, AREG, EDA2R and GDF15, AREG, GDF15 and TNC, CEACAM5, SERPINA1 and TNC, AREG, FCRL1 and TNC, AREG, CEACAM5 and EDA2R, AREG, CEACAM5 and FCRL1, CEACAM5, EDA2R and TNC, EDA2R, GDF15 and SERPINA1, AREG, PT X3 and SERPINA1, EDA2R, GDF15 and TNC, FCRL1, SERPINA1 and TNC, AREG, FCRL1 and SERPINA1, AREG, GDF15 and SERPINA1, AREG, CEACAM5 and SERPINA1, AREG, CEACAM5 and TNC, AREG, EDA2R and SERPINA1, EDA2R, SERPINA1 and TNC, AREG, EDA2R and TNC, or AREG, SERPINA1 and TNC.
优选地，所述A包含4markers组合，所述4markers组合为所述B中的任意4种。Preferably, A comprises a combination of 4 markers, and the combination of 4 markers is any 4 of B.
优选地，所述4markers组合为b1)和b2):Preferably, the 4 markers are combined into b1) and b2):
b1)所述3markers组合(优选上述622个3markers组合中的任意一种)；b1) the 3markers combination (preferably any one of the above 622 3markers combinations);
b2)所述B中的任意一种；b2) any one of the above B;
所述b2)不同于b1)中所述3markers组合中的任意一个marker。The b2) is different from any one of the markers in the combination of 3 markers in b1).
优选地，所述4markers组合为：ADGRE1、GDF15、PTX3与THBS4，PTX3、HMCN2、POF1B与FASLG，SPP1、COMP、LMNB2与FCRL1，ADGRE1、GDF15、PTX3与COMP，AREG、CEACAM5、ADAMTS8与DCTPP1，SPP1、FCRL1、SOD3与ADGRE5，PTX3、GDF15、ADGRG2与ADGRE5，TMPRSS15、SPP1、FCRL1与SOD3，AREG、CEACAM5、ADAMTS8与TNFRSF11A，GNAS、LMNB2、PLXDC2与PROK1，NOTCH1、COMP、GDF15与PTX3，ADGRE1、GDF15、PTX3与ADGRG2，TMPRSS15、PTX3、GDF15与THBS4，PTX3、GDF15、COMP与RET，AREG、CEACAM5、ADAMTS8与CNTN1，ADGRE2、SOD3、SPP1与LMNB2，ADGRE2、SOD3、SPP1与TCL1A，TMPRSS15、PTX3、SPP1与THBS4，TMPRSS15、SPP1、SOD3与MMP12，TMPRSS15、SPP1、COMP与FCRL1，CEACAM5、COMP、GDF15与PTX3，SPP1、COMP、FCRL1与SOD3，ADGRE1、GDF15、PTX3与NOTCH3，PTX3、GDF15、THBS4与ADGRE5，PTX3、POF1B、THBS4与FASLG，TMPRSS15、PTX3、GDF15与COMP，PTX3、GDF15、RET与ADGRG2，SPP1、ENPP6、FCRL1与ADGRE5，NOTCH3、ESM1、PLXDC2与LMNB2，CEACAM5、GDF15、NOTCH1与PTX3，SPP1、PLXDC2、COMP与LMNB2，SPP1、PLXDC2、FCRL1与SOD3，ITGA11、LMNB2、RET与SOD3，TMPRSS15、COMP、PTX3与PGA4，PTX3、GDF15、PLXDC2与THBS4，CRTAC1、SPP1、TCL1A与SOD3，TMPRSS15、SPP1、COMP与IL4R，ADGRE2、SOD3、SPP1与PROK1，PTX3、GDF15、THBS4与ADGRG2，ADGRE1、GDF15、PTX3与GSN，PTX3、GDF15、THBS4与EXTL1，SPP1、COMP、FCRL1与ADGRE5，NT5C1A、TMPRSS15、COMP与SPP1，SPP1、COMP、FCRL1与IL4R，ADGRE1、GDF15、PTX3与CNTN4，PTX3、ITGA11、POF1B与THBS4，ADGRE2、SOD3、SPP1与TNFRSF11A，PTX3、ENPP6、THBS4与FASLG，PTX3、POF1B、THBS4与EXTL1，TMPRSS15、SPP1、SOD3与EXTL1，SPP1、LMNB2、FCRL1与SOD3，TMPRSS15、SPP1、COMP与CLEC3B，COMP、FCRL1、PTX3与SPP1，ADGRE1、GDF15、PTX3与ADGRE2，NOTCH1、COMP、GDF15与C9，ADGRE1、GDF15、PTX3与BMP4，PTX3、SPP1、COMP与FCRL1，SPP1、PLXDC2、COMP与IL4R，PTX3、SPP1、ENPP6与COMP，TMPRSS15、SPP1、COMP与TNFRSF10B，SPP1、COMP、LMNB2与FASLG，ADGRE1、CRTAC1、GDF15与PTX3，AREG、COMP、EDA2R与TMPRSS15，COMP、LMNB2、FCRL1与MMP12，PTX3、GDF15、PLXDC2与ADGRE5，SPP1、ENPP6、COMP与FCRL1，SPP1、THBS4、LMNB2与ADGRE5，SPP1、COMP、FCRL1与CLEC3B，SPP1、COMP、LMNB2与SOD3，ADGRE1、GDF15、PTX3与ITGA2，PTX3、GDF15、THBS4与FASLG，TMPRSS15、SPP1、THBS4与FCRL1，ADGRE1、GDF15、PTX3与NOTCH1，PTX3、COMP、POF1B与FASLG，PTX3、GDF15、COMP与THBS4，DCC、COMP、SPP1与PROK1，ADGRE1、GDF15、PTX3与TMPRSS15，PTX3、PLXDC2、POF1B与FASLG，GDF15、PLXDC2、LMNB2与DLK1，GDF15、COMP、LMNB2与DLK1，SPP1、LMNB2、SOD3与ADGRE5，CEACAM5、COMP、PTX3与PGA4，GSN、TMPRSS15、PGA4与PTX3，PTX3、GDF15、ITGA11与THBS4，ADGRE1、KRT19、LMNB2与COMP，PTX3、GDF15、COMP与POF1B，SPP1、ADGRG2、FCRL1与SOD3，ADGRE1、GDF15、PTX3与PKD1，ADGRE1、KRT19、LMNB2与ITGA2，ADGRE1、GDF15、PTX3与ADGRE5，TMPRSS15、THBS4、CLEC3B与TNFRSF10B，TMPRSS15、SPP1、RET与SOD3，PTX3、THBS4、LMNB2与CNTN4，PTX3、GDF15、THBS4与RET，TMPRSS15、PTX3、FASLG与MMP12，SPP1、ITGA11、FCRL1与SOD3，PTX3、GDF15、COMP与EXTL1，TMPRSS15、COMP、MMP12与IL4R，PTX3、GDF15、THBS4与CNTN4，COMP、FCRL1、GDF15与NOTCH1，TMPRSS15、PTX3、POF1B与THBS4，SPP1、COMP、FASLG与FCRL1，PTX3、THBS4、FASLG与IL4R，PTX3、GDF15、THBS4与FCRL1，ADGRE1、GDF15、PTX3与HMCN2，NOTCH1、COMP、GDF15与SPP1，PTX3、KRT19、FASLG与ADGRG2，PTX3、ITGA11、POF1B与EXTL1，SPP1、RET、FCRL1与SOD3，SPP1、HMCN2、FCRL1与SOD3，PTX3、GDF15、PLXDC2与RET，TMPRSS15、SPP1、SOD3与IL4R，PTX3、SPP1、COMP与CNTN4，COMP、GDF15、PTX3与TNC，NOTCH3、ESM1、PLXDC2与GDF15，TMPRSS15、COMP、PTX3与SPP1，ADGRE1、GDF15、PTX3与ADAMTS8，PTX3、GDF15、COMP与ADGRG2，CRTAC1、SPP1、TCL1A与NOTCH1，TMPRSS15、SOD3、MMP12与IL4R，PTX3、GDF15、ENPP6与THBS4，TMPRSS15、PTX3、POF1B与FASLG，TMPRSS15、SPP1、FASLG与CLEC3B，TMPRSS15、PTX3、THBS4与LMNB2，TMPRSS15、PTX3、SPP1与SOD3，ADGRE2、SOD3、SPP1与FCRL1，SPP1、LMNB2、CLEC3B与ADGRE5，SPP1、COMP、ADGRE5与IL4R，ITGA11、LMNB2、FCRL1与SOD3，PTX3、POF1B、THBS4与ADGRE5，CD48、CLEC3B、SPP1与TNFRSF10B，ADGRE1、GDF15、PTX3与AGR3，SPP1、ADGRG2、FCRL1与ADGRE5，PTX3、GDF15、COMP与ADGRE5，ADGRE2、SOD3、SPP1与IL4R，PTX3、SPP1、FCRL1与SOD3，SPP1、COMP、TNFRSF10B与ADGRE5，SPP1、CLEC3B、TNFRSF10B与ADGRE5，ADGRE1、CRTAC1、GDF15与TMPRSS15，TMPRSS15、SPP1、COMP与MMP12，PTX3、GDF15、POF1B与THBS4，SPP1、FASLG、SOD3与ADGRE5，PTX3、SPP1、ITGA11与SOD3，PTX3、POF1B、THBS4与RET，PTX3、GDF15、THBS4与CLEC3B，TMPRSS15、COMP、LMNB2与MMP12，ADGRE1、GDF15、PTX3与ITGAM，CD48、CLEC3B、SPP1与EDA2R，SPP1、FCRL1、SOD3与ITGA2，SPP1、COMP、LMNB2与ITGB1，ADGRE1、KRT19、LMNB2与TMPRSS15，PTX3、ITGA11、POF1B与RET，PTX3、POF1B、THBS4与FCRL1，TMPRSS15、SPP1、ITGA11与SOD3，SPP1、COMP、ITGA11与FCRL1，PTX3、PLXDC2、POF1B与RET，TMPRSS15、SPP1、FASLG与SOD3，DCC、CNTN4、PTX3与PGA4，CRTAC1、SPP1、TCL1A与LMNB2，PTX3、GDF15、HMCN2与ADGRE5，PTX3、SPP1、COMP与IL4R，TMPRSS15、PTX3、THBS4与FASLG，GNAS、NT5C1A、TMPRSS15与AREG，COMP、FCRL1、PTX3与POF1B，PTX3、COMP、POF1B与CNTN4，TMPRSS15、PTX3、SPP1与COMP，TMPRSS15、PTX3、COMP与POF1B，NOTCH1、COMP、GDF15与ADGRE1，PTX3、GDF15、COMP与FASLG，CRTAC1、SPP1、TCL1A与ADGRE5，SPP1、LMNB2、FCRL1与ADGRE5，SPP1、ENPP6、COMP与TNFRSF10B，SPP1、COMP、ADGRG2与FCRL1，NOTCH3、ESM1、PLXDC2与EDA2R，PTX3、SPP1、ENPP6与ADGRE5，SPP1、FCRL1、CLEC3B与ADGRE5，NT5C1A、THBS4、PTX3与EXTL1，ADGRE2、SOD3、SPP1与FASLG，TMPRSS15、SPP1、PLXDC2与SOD3，DCC、COMP、SPP1与PLXDC2，CD48、CLEC3B、SPP1与LMNB2，ADGRE1、GDF15、PTX3与ITGB1，SPP1、COMP、FASLG与ADGRE5，TMPRSS15、PTX3、GDF15与FASLG，COMP、FCRL1、GDF15与TMPRSS15，TMPRSS15、SPP1、COMP与SOD3，TMPRSS15、SPP1、PLXDC2与COMP，SPP1、COMP、FCRL1与DLK1，GDF15、NOTCH1、PTX3与TMPRSS15，PTX3、GDF15、COMP与LMNB2，SPP1、PLXDC2、COMP与FCRL1，PTX3、COMP、POF1B与RET，PTX3、GDF15、COMP与HMCN2，COMP、FCRL1、PTX3与EDA2R，GDF15、SPP1、PLXDC2与COMP，TMPRSS15、SPP1、SOD3与ADGRE5，PTX3、POF1B、FASLG与CNTN4，TMPRSS15、PTX3、THBS4与TNFRSF10B，TMPRSS15、SPP1、COMP与FASLG，TMPRSS15、GDF15、SPP1与COMP，CEACAM5、COMP、GDF15与TNC，PTX3、GDF15、POF1B与ADGRE5，SPP1、FCRL1、SOD3与MMP12，PTX3、GDF15、SPP1与COMP，PTX3、PLXDC2、POF1B与FCRL1，CRTAC1、NOTCH1、GDF15与SPP1，ADGRE1、GDF15、PTX3与POF1B，SPP1、SOD3、TNFRSF10B与ADGRE5，GDF15、COMP、LMNB2与FCRL1，TMPRSS15、SPP1、THBS4与TNFRSF10B，CRTAC1、NOTCH1、GDF15与PTX3，SPP1、THBS4、FCRL1与SOD3，PTX3、PLXDC2、THBS4与IL4R，ADGRE2、SOD3、SPP1与TMPRSS15，TMPRSS15、LMNB2、SOD3与MMP12，PTX3、SPP1、COMP与POF1B，TMPRSS15、SPP1、THBS4与SOD3，CRTAC1、SPP1、TCL1A与ADGRE2，TMPRSS15、SPP1、THBS4与LMNB2，PTX3、POF1B、THBS4与CNTN4，PTX3、GDF15、THBS4与IL4R，ADGRE1、GDF15、PTX3与BAG3，SPP1、FCRL1、SOD3与IL4R，PTX3、LMNB2、SOD3与CNTN4，PTX3、PLXDC2、POF1B与THBS4，TMPRSS15、GDF15、THBS4与MMP12，TMPRSS15、THBS4、MMP12与IL4R，SPP1、KRT19、COMP与FCRL1，COMP、EDA2R、PTX3与TMPRSS15，SPP1、PLXDC2、COMP与POF1B，ITGA11、POF1B、RET与SOD3，PTX3、GDF15、ADGRG2与CNTN4，PTX3、GDF15、THBS4与SOD3，PTX3、SPP1、THBS4与CNTN4，SPP1、COMP、POF1B与FCRL1，SPP1、THBS4、CLEC3B与ADGRE5，TMPRSS15、PTX3、THBS4与MMP12，TMPRSS15、GDF15、COMP与LMNB2，PTX3、GDF15、THBS4与ITGB1，ADGRE1、GDF15、PTX3与RET，PTX3、HMCN2、POF1B与SOD3，PTX3、PLXDC2、POF1B与SOD3，PTX3、GDF15、HMCN2与ADGRG2，COMP、FCRL1、GDF15与PTX3，SPP1、ADGRG2、SOD3与ADGRE5，ADGRE1、GDF15、PTX3与ENPP6，TMPRSS15、THBS4、LMNB2与MMP12，SPP1、ENPP6、ITGA11与ADGRE5，ADGRE1、GDF15、PTX3与SOD3，SPP1、COMP、LMNB2与ADGRE5，TMPRSS15、PTX3、THBS4与IL4R，SPP1、COMP、CEACAM5与SOD3，SPP1、COMP、FCRL1与ITGB1，FCRL1、GDF15、NOTCH1与PTX3，SPP1、COMP、LMNB2与ADGRG2，PTX3、COMP、HMCN2与POF1B，DCC、COMP、SPP1与TMPRSS15，TMPRSS15、PTX3、COMP与TNFRSF10B，TMPRSS15、PTX3、KRT19与ENPP6，PTX3、SPP1、PLXDC2与POF1B，NOTCH1、COMP、GDF15与TCL1A，ADGRE2、SOD3、SPP1与ITGA11，DCC、COMP、SPP1与PTX3，PTX3、GDF15、ADGRG2与FCRL1，TMPRSS15、POF1B、FASLG与MMP12，PTX3、POF1B、FCRL1与SOD3，PTX3、POF1B、RET与SOD3，TMPRSS15、PTX3、KRT19与EXTL1，PTX3、GDF15、PLXDC2与COMP，PTX3、GDF15、ITGA11与RET，PTX3、SPP1、COMP与RET，ADGRE2、SOD3、SPP1与CEACAM16，TMPRSS15、SPP1、KRT19与COMP，PTX3、ITGA11、POF1B与SOD3，TMPRSS15、COMP、FCRL1与TNFRSF10B，TMPRSS15、PTX3、GDF15与PLXDC2，PTX3、COMP、LMNB2与RET，PTX3、THBS4、ADGRG2与IL4R，PTX3、GDF15、COMP与DLK1，SPP1、RET、ADGRG2与SOD3，GDF15、LMNB2、ADGRG2与DLK1，COMP、GDF15、NOTCH1与SERPINA1，TMPRSS15、SPP1、ADGRG2与SOD3，PTX3、COMP、POF1B与FCRL1，TMPRSS15、SPP1、COMP与EXTL1，NT5C1A、THBS4、PTX3与CNTN4，PTX3、COMP、TNFRSF10B与CNTN4，ADGRE2、SOD3、SPP1与CEACAM5，PTX3、POF1B、SOD3与EXTL1，TMPRSS15、PTX3、POF1B与FCRL1，COMP、GDF15、TMPRSS15与TNC，TMPRSS15、COMP、PTX3与TNFRSF10B，GNAS、NT5C1A、TMPRSS15与ITGA11，TMPRSS15、PTX3、GDF15与KRT19，ADGRE2、SOD3、SPP1与PTX3，PTX3、SPP1、PLXDC2与COMP，TMPRSS15、SPP1、LMNB2与SOD3，PTX3、SPP1、THBS4与ADGRE5，PTX3、SPP1、COMP与LMNB2，ADGRE1、LMNB2、THBS4与TMPRSS15，GDF15、SPP1、COMP与FCRL1，GNAS、NT5C1A、TMPRSS15与PTX3，PTX3、SPP1、COMP与TNFRSF10B，PTX3、COMP、POF1B与EXTL1，NOTCH1、SPP1、TNFRSF10B与COMP，SPP1、ENPP6、CLEC3B与ADGRE5，ADGRE2、SOD3、SPP1与COMP，NOTCH1、COMP、GDF15与PROK1，PTX3、HMCN2、POF1B与EXTL1，SPP1、PLXDC2、SOD3与IL4R，PTX3、POF1B、ITGB7与EXTL1，COMP、LMNB2、FCRL1与SOD3，SPP1、COMP、FASLG与CLEC3B，ADGRE2、SOD3、SPP1与PGA4，COMP、FCRL1、PTX3与PGA4，PTX3、GDF15、SOD3与ADGRE5，SPP1、COMP、SOD3与IL4R，TMPRSS15、PTX3、GDF15与CNTN4，SPP1、ENPP6、CEACAM5与ADGRE5，SPP1、ITGA11、ADGRG2与ADGRE5，PTX3、SPP1、COMP与FASLG，PTX3、POF1B、THBS4与ITGA2，PTX3、SPP1、COMP与ADGRE5，GDF15、PLXDC2、CEACAM5与ADGRE5，PTX3、GDF15、PLXDC2与DLK1，TMPRSS15、THBS4、LMNB2与CLEC3B，ADGRE1、LMNB2、THBS4与CLEC3B，GSN、SPP1、THBS4与PTX3，TMPRSS15、SPP1、THBS4与CLEC3B，PTX3、GDF15、POF1B与CNTN4，SPP1、FCRL1、SOD3与ITGB1，或ADGRE2、SOD3、SPP1与PLXDC1；即上述332个4markers组合中的任一种。Preferably, the 4 markers combination is: ADGRE1, GDF15, PTX3 and THBS4, PTX3, HMCN2, POF1B and FASLG, SPP1, COMP, LMNB2 and FCRL1, ADGRE1, GDF15, PTX3 and COMP, AREG, CEACAM5, ADAMTS8 and DCTPP1, SPP1, FCRL1, SOD3 and ADGRE5, PTX3, GDF15, ADGRG2 and ADGRE5, TMPRSS15, SPP1, FCRL1 and SOD3, AREG, CEACAM5, ADAMTS8 and TNFRSF11A, GNAS, L MNB2, PLXDC2 and PROK1, NOTCH1, COMP, GDF15 and PTX3, ADGRE1, GDF15, PTX3 and ADGRG2, TMPRSS15, PTX3, GDF15 and THBS4, PTX3, GDF15, COMP and RET, AREG, CEACAM5, ADAMTS8 and CNTN1, ADGRE2, SOD3, SPP1 and LMNB2, ADGRE2, SOD3, SPP1 and TCL1A, TMPRSS15, PTX3, SPP1 and THBS4, TMPRSS15, SPP1, SOD3 and MMP12, TMPRSS15, SPP1, COMP and FCRL1, CEACAM5, COMP, GDF15 and PTX3, SPP1, COMP, FCRL1 and SOD3, ADGRE1, GDF15, PTX3 and NOTCH3, PTX3, GDF15, THBS4 and ADGRE5, PTX3, POF1B, THBS4 and FASLG, TMPRSS15, PTX3, GDF15 and COMP, PTX3, GDF15, RET and ADGRG2, SPP1, ENPP6, FCRL1 and ADGRE5, NOTCH3, ESM1, PLXDC2 and LMNB2, CEACAM5 GDF15, NOTCH1 and PTX 3, SPP1, PLXDC2, COMP and LMNB2, SPP1, PLXDC2, FCRL1 and SOD3, ITGA11, LMNB2, RET and SOD3, TMPRSS15, COMP, PTX3 and PGA4, PTX3, GDF15, PLXDC2 and THBS4, CRTAC1, SPP1, TCL1A and SOD3, TMPRSS15, SPP1, COMP and IL4R, ADGRE2, SOD3, SPP1 and PROK1, PTX3, GDF15, THBS4 and ADGRG2, ADGRE1, GDF15, PTX3 and GSN, PTX3, GDF15, THBS 4 and EXTL1, SPP1, COMP, FCRL1 and ADGRE5, NT5C1A, TMPRSS15, COMP and SPP1, SPP1, COMP, FCRL1 and IL4R, ADGRE1, GDF15, PTX3 and CNTN4, PTX3, ITGA11, POF1B and THBS4, ADGRE2, SOD3, SPP1 and TNFRSF11A, PTX3, ENPP6, THBS4 and FASLG, PTX3, POF1B, THBS4 and EXTL1, TMPRSS15, SPP1, SOD3 and EXTL1, SPP1, LMNB2, FCRL1 and SOD3, TM PRSS15, SPP1, COMP and CLEC3B, COMP, FCRL1, PTX3 and SPP1, ADGRE1, GDF15, PTX3 and ADGRE2, NOTCH1, COMP, GDF15 and C9, ADGRE1, GDF15, PTX3 and BMP4, PTX3, SPP1, COMP and FCRL1, SPP1, PLXDC2, COMP and IL4R, PTX3, SPP1, ENPP6 and COMP, TMPRSS15, SPP1, COMP and TNFRSF10B, SPP1, COMP, LMNB2 and FASLG, ADGRE1, CRTAC1, GDF15 and PTX3, AREG, COMP, EDA2R and TMPRSS15, COMP, LMNB2, FCRL1 and MMP12, PTX3, GDF15, PLXDC2 and ADGRE5, SPP1, ENPP6, COMP and FCRL1, SPP1, THBS4, LMNB2 and ADGRE5, SPP1, COMP, FCRL1 and CLEC3B, SPP1, COMP, LMNB2 and SOD3, ADGRE1, GDF15, PTX3 and ITGA2, PTX3, GDF15, THBS4 and FASLG, TMPRSS15, SPP1, THBS4 and FCRL1, ADGRE1, GDF15, PTX3 and NOTCH1, PTX3, COMP, POF1B and FASLG, PTX3, GDF15, COMP and THBS4, DCC, COMP, SPP1 and PROK1, ADGRE1, GDF15, PTX3 and TMPRSS15, PTX3, PLXDC2, POF1B and FASLG, GDF15, PLXDC2, LMNB2 and DLK1, GDF15, COMP, LMNB2 and DLK1, SPP1, LMNB2, SOD3 and ADGRE5, CEACAM5, COMP, PTX3 and PGA4, GSN, TMPRSS15, PGA4 and PTX3, P TX3, GDF15, ITGA11 and THBS4, ADGRE1, KRT19, LMNB2 and COMP, PTX3, GDF15, COMP and POF1B, SPP1, ADGRG2, FCRL1 and SOD3, ADGRE1, GDF15, PTX3 and PKD1, ADGRE1, KRT19, LMNB2 and ITGA2, ADGRE1, GDF15, PTX3 and ADGRE5, TMPRSS15, THBS4, CLEC3B and TNFRSF10B, TMPRSS15, SPP1, RET and SOD3, PTX3, THBS4, LMNB2 and CNTN4, PTX3, GDF15, THBS4 and RET, TMPRSS15, PTX3, FASLG and MMP12, SPP1, ITGA11, FCRL1 and SOD3, PTX3, GDF15, COMP and EXTL1, TMPRSS15, COMP, MMP12 and IL4R, PTX3, GDF15, THBS4 and CNTN4, COMP, FCRL1, GDF15 and NOTCH1, TMPRSS15, PTX3, POF1B and THBS4, SPP1, COMP, FASLG and FCRL1, PTX3, THBS4, FASLG and IL4R, PTX3, GDF15, THBS4 and FCR L1, ADGRE1, GDF15, PTX3 and HMCN2, NOTCH1, COMP, GDF15 and SPP1, PTX3, KRT19, FASLG and ADGRG2, PTX3, ITGA11, POF1B and EXTL1, SPP1, RET, FCRL1 and SOD3, SPP1, HMCN2, FCRL1 and SOD3, PTX3, GDF15, PLXDC2 and RET, TMPRSS15, SPP1, SOD3 and IL4R, PTX3, SPP1, COMP and CNTN4, COMP, GDF15, PTX3 and TNC, NOTCH3, ESM1, PLXDC2 and GD F15, TMPRSS15, COMP, PTX3 and SPP1, ADGRE1, GDF15, PTX3 and ADAMTS8, PTX3, GDF15, COMP and ADGRG2, CRTAC1, SPP1, TCL1A and NOTCH1, TMPRSS15, SOD3, MMP12 and IL4R, PTX3, GDF15, ENPP6 and THBS4, TMPRSS15, PTX3, POF1B and FASLG, TMPRSS15, SPP1, FASLG and CLEC3B, TMPRSS15, PTX3, THBS4 and LMNB2, TMPRSS15, PTX3, SPP1 and S OD3, ADGRE2, SOD3, SPP1 and FCRL1, SPP1, LMNB2, CLEC3B and ADGRE5, SPP1, COMP, ADGRE5 and IL4R, ITGA11, LMNB2, FCRL1 and SOD3, PTX3, POF1B, THBS4 and ADGRE5, CD48, CLEC3B, SPP1 and TNFRSF10B, ADGRE1, GDF15, PTX3 and AGR3, SPP1, ADGRG2, FCRL1 and ADGRE5, PTX3, GDF15, COMP and ADGRE5, ADGRE2, SOD3, SPP1 and IL4R, PTX3, S PP1, FCRL1 and SOD3, SPP1, COMP, TNFRSF10B and ADGRE5, SPP1, CLEC3B, TNFRSF10B and ADGRE5, ADGRE1, CRTAC1, GDF15 and TMPRSS15, TMPRSS15, SPP1, COMP and MMP12, PTX3, GDF15, POF1B and THBS4, SPP1, FASLG, SOD3 and ADGRE5, PTX3, SPP1, ITGA11 and SOD3, PTX3, POF1B, THBS4 and RET, PTX3, GDF15, THBS4 and CLEC3B, TMPRSS15, CO MP, LMNB2 and MMP12, ADGRE1, GDF15, PTX3 and ITGAM, CD48, CLEC3B, SPP1 and EDA2R, SPP1, FCRL1, SOD3 and ITGA2, SPP1, COMP, LMNB2 and ITGB1, ADGRE1, KRT19, LMNB2 and TMPRSS15, PTX3, ITGA11, POF1B and RET, PTX3, POF1B, THBS4 and FCRL1, TMPRSS15, SPP1, ITGA11 and SOD3, SPP1, COMP, ITGA11 and FCRL1, PTX3, PLXDC2, POF1B and RE T, TMPRSS15, SPP1, FASLG and SOD3, DCC, CNTN4, PTX3 and PGA4, CRTAC1, SPP1, TCL1A and LMNB2, PTX3, GDF15, HMCN2 and ADGRE5, PTX3, SPP1, COMP and IL4R, TMPRSS15, PTX3, THBS4 and FASLG, GNAS, NT5C1A, TMPRSS15 and AREG, COMP, FCRL1, PTX3 and POF1B, PTX3, COMP, POF1B and CNTN4, TMPRSS15, PTX3, SPP1 and COMP, TMPRSS15, PTX3, COMP and POF1B, NOTCH1, COMP, GDF15 and ADGRE1, PTX3, GDF15, COMP and FASLG, CRTAC1, SPP1, TCL1A and ADGRE5, SPP1, LMNB2, FCRL1 and ADGRE5, SPP1, ENPP6, COMP and TNFRSF10B, SPP1, COMP, ADGRG2 and FCRL1, NOTCH3, ESM1, PLXDC2 and EDA2R, PTX3, SPP1, ENPP6 and ADGRE5, SPP1, FCRL1, CLEC3B and ADGRE5, NT5C1A, THBS4, PTX3 and E XTL1, ADGRE2, SOD3, SPP1 and FASLG, TMPRSS15, SPP1, PLXDC2 and SOD3, DCC, COMP, SPP1 and PLXDC2, CD48, CLEC3B, SPP1 and LMNB2, ADGRE1, GDF15, PTX3 and ITGB1, SPP1, COMP, FASLG and ADGRE5, TMPRSS15, PTX3, GDF15 and FASLG, COMP, FCRL1, GDF15 and TMPRSS15, TMPRSS15, SPP1, COMP and SOD3, TMPRSS15, SPP1, PLXDC2 and COMP, SP P1, COMP, FCRL1 and DLK1, GDF15, NOTCH1, PTX3 and TMPRSS15, PTX3, GDF15, COMP and LMNB2, SPP1, PLXDC2, COMP and FCRL1, PTX3, COMP, POF1B and RET, PTX3, GDF15, COMP and HMCN2, COMP, FCRL1, PTX3 and EDA2R, GDF15, SPP1, PLXDC2 and COMP, TMPRSS15, SPP1, SOD3 and ADGRE5, PTX3, POF1B, FASLG and CNTN4, TMPRSS15, PTX3, THBS4 and T NFRSF10B, TMPRSS15, SPP1, COMP and FASLG, TMPRSS15, GDF15, SPP1 and COMP, CEACAM5, COMP, GDF15 and TNC, PTX3, GDF15, POF1B and ADGRE5, SPP1, FCRL1, SOD3 and MMP12, PTX3, GDF15, SPP1 and COMP, PTX3, PLXDC2, POF1B and FCRL1, CRTAC1, NOTCH1, GDF15 and SPP1, ADGRE1, GDF15, PTX3 and POF1B, SPP1, SOD3, TNFRSF10B and ADGRE5, GDF15, COMP, LMNB2 and FCRL1, TMPRSS15, SPP1, THBS4 and TNFRSF10B, CRTAC1, NOTCH1, GDF15 and PTX3, SPP1, THBS4, FCRL1 and SOD3, PTX3, PLXDC2, THBS4 and IL4R, ADGRE2, SOD3, SPP1 and TMPRSS15, TMPRSS15, LMNB2, SOD3 and MMP12, PTX3, SPP1, COMP and POF1B, TMPRSS15, SPP1, THBS4 and SOD3, CRTAC1, SPP1, TCL1A and ADGRE2, TM PRSS15, SPP1, THBS4 and LMNB2, PTX3, POF1B, THBS4 and CNTN4, PTX3, GDF15, THBS4 and IL4R, ADGRE1, GDF15, PTX3 and BAG3, SPP1, FCRL1, SOD3 and IL4R, PTX3, LMNB2, SOD3 and CNTN4, PTX3, PLXDC2, POF1B and THBS4, TMPRSS15, GDF15, THBS4 and MMP12, TMPRSS15, THBS4, MMP12 and IL4R, SPP1, KRT19, COMP and FCRL1, COMP, EDA2R, PTX3 and TMPRSS15, SPP1, PLXDC2, COMP and POF1B, ITGA11, POF1B, RET and SOD3, PTX3, GDF15, ADGRG2 and CNTN4, PTX3, GDF15, THBS4 and SOD3, PTX3, SPP1, THBS4 and CNTN4, SPP1, COMP, POF1B and FCRL1, SPP1, THBS4, CLEC3B and ADGRE5, TMPRSS15, PTX3, THBS4 and MMP12, TMPRSS15, GDF15, COMP and LMNB2, PTX3, GDF15, THBS4 and ITGB1, ADG RE1, GDF15, PTX3 and RET, PTX3, HMCN2, POF1B and SOD3, PTX3, PLXDC2, POF1B and SOD3, PTX3, GDF15, HMCN2 and ADGRG2, COMP, FCRL1, GDF15 and PTX3, SPP1, ADGRG2, SOD3 and ADGRE5, ADGRE1, GDF15, PTX3 and ENPP6, TMPRSS15, THBS4, LMNB2 and MMP12, SPP1, ENPP6, ITGA11 and ADGRE5, ADGRE1, GDF15, PTX3 and SOD3, SPP1, COMP, LMNB2 and ADGRE5, TMPRSS15, PTX3, THBS4 and IL4R, SPP1, COMP, CEACAM5 and SOD3, SPP1, COMP, FCRL1 and ITGB1, FCRL1, GDF15, NOTCH1 and PTX3, SPP1, COMP, LMNB2 and ADGRG2, PTX3, COMP, HMCN2 and POF1B, DCC, COMP, SPP1 and TMPRSS15, TMPRSS15, PTX3, COMP and TNFRSF10B, TMPRSS15, PTX3, KRT19 and ENPP6, PTX3, SPP1, PLXDC2 and POF1B, N OTCH1, COMP, GDF15 and TCL1A, ADGRE2, SOD3, SPP1 and ITGA11, DCC, COMP, SPP1 and PTX3, PTX3, GDF15, ADGRG2 and FCRL1, TMPRSS15, POF1B, FASLG and MMP12, PTX3, POF1B, FCRL1 and SOD3, PTX3, POF1B, RET and SOD3, TMPRSS15, PTX3, KRT19 and EXTL1, PTX3, GDF15, PLXDC2 and COMP, PTX3, GDF15, ITGA11 and RET, PTX3, SPP1, COMP and RET, ADGRE2, SOD3, SPP1 and CEACAM16, TMPRSS15, SPP1, KRT19 and COMP, PTX3, ITGA11, POF1B and SOD3, TMPRSS15, COMP, FCRL1 and TNFRSF10B, TMPRSS15, PTX3, GDF15 and PLXDC2, PTX3, COMP, LMNB2 and RET, PTX3, THBS4, ADGRG2 and IL4R, PTX3, GDF15, COMP and DLK1, SPP1, RET, ADGRG2 and SOD3, GDF15, LMNB2, ADGRG2 and DLK1, COMP, GDF 15, NOTCH1 and SERPINA1, TMPRSS15, SPP1, ADGRG2 and SOD3, PTX3, COMP, POF1B and FCRL1, TMPRSS15, SPP1, COMP and EXTL1, NT5C1A, THBS4, PTX3 and CNTN4, PTX3, COMP, TNFRSF10B and CNTN4, ADGRE2, SOD3, SPP1 and CEACAM5, PTX3, POF1B, SOD3 and EXTL1, TMPRSS15, PTX3, POF1B and FCRL1, COMP, GDF15, TMPRSS15 and TNC, TMPRSS15, C OMP, PTX3 and TNFRSF10B, GNAS, NT5C1A, TMPRSS15 and ITGA11, TMPRSS15, PTX3, GDF15 and KRT19, ADGRE2, SOD3, SPP1 and PTX3, PTX3, SPP1, PLXDC2 and COMP, TMPRSS15, SPP1, LMNB2 and SOD3, PTX3, SPP1, THBS4 and ADGRE5, PTX3, SPP1, COMP and LMNB2, ADGRE1, LMNB2, THBS4 and TMPRSS15, GDF15, SPP1, COMP and FCRL1, GNAS, NT5C1A, TMPRSS15 and PTX3, PTX3, SPP1, COMP and TNFRSF10B, PTX3, COMP, POF1B and EXTL1, NOTCH1, SPP1, TNFRSF10B and COMP, SPP1, ENPP6, CLEC3B and ADGRE5, ADGRE2, SOD3, SPP1 and COMP, NOTCH1, COMP, GDF15 and PROK1, PTX3, HMCN2, POF1B and EXTL1, SPP1, PLXDC2, SOD3 and IL4R, PTX3, POF1B, ITGB7 and EXTL1, COMP, LMNB2, FCRL1 and SOD3, SPP1, COMP, FASLG and CLEC3B, ADGRE2, SOD3, SPP1 and PGA4, COMP, FCRL1, PTX3 and PGA4, PTX3, GDF15, SOD3 and ADGRE5, SPP1, COMP, SOD3 and IL4R, TMPRSS15, PTX3, GDF15 and CNTN4, SPP1, ENPP6, CEACAM5 and ADGRE5, SPP1, ITGA11, ADGRG2 and ADGRE5, PTX3, SPP1, COMP and FASLG, PTX3, POF1B, THBS4 and ITGA2, PTX3, SPP1, COMP and ADG RE5, GDF15, PLXDC2, CEACAM5 and ADGRE5, PTX3, GDF15, PLXDC2 and DLK1, TMPRSS15, THBS4, LMNB2 and CLEC3B, ADGRE1, LMNB2, THBS4 and CLEC3B, GSN, SPP1, THBS4 and PTX3, TMPRSS15, SPP1, THBS4 and CLEC3B, PTX3, GDF15, POF1B and CNTN4, SPP1, FCRL1, SOD3 and ITGB1, or ADGRE2, SOD3, SPP1 and PLXDC1; that is, any of the 332 4markers combinations mentioned above.
优选地，所述4markers组合为所述E中的任意4种。Preferably, the 4 markers are combined into any 4 of the E.
优选地，所述4markers组合为：NOTCH1、COMP、GDF15与PTX3，CEACAM5、COMP、GDF15与PTX3，TMPRSS15、PTX3、GDF15与COMP，CEACAM5、GDF15、NOTCH1与PTX3，AREG、COMP、EDA2R与TMPRSS15，COMP、FCRL1、GDF15与NOTCH1，COMP、GDF15、PTX3与TNC，COMP、FCRL1、GDF15与TMPRSS15，GDF15、NOTCH1、PTX3与TMPRSS15，CEACAM5、COMP、GDF15与TNC，COMP、EDA2R、PTX3与TMPRSS15，COMP、FCRL1、GDF15与PTX3，FCRL1、GDF15、NOTCH1与PTX3，COMP、GDF15、NOTCH1与SERPINA1，COMP、GDF15、TMPRSS15与TNC，AREG、CEACAM5、COMP与EDA2R，AREG、CEACAM5、COMP与FCRL1，AREG、CEACAM5、COMP与GDF15，AREG、CEACAM5、COMP与NOTCH1，AREG、CEACAM5、COMP与PTX3，AREG、CEACAM5、COMP与SERPINA1，AREG、CEACAM5、COMP与TMPRSS15，AREG、CEACAM5、COMP与TNC，AREG、CEACAM5、EDA2R与FCRL1，AREG、CEACAM5、EDA2R与GDF15，AREG、CEACAM5、EDA2R与NOTCH1，AREG、CEACAM5、EDA2R与PTX3，AREG、CEACAM5、EDA2R与SERPINA1，AREG、CEACAM5、EDA2R与TMPRSS15，AREG、CEACAM5、EDA2R与TNC，AREG、CEACAM5、FCRL1与GDF15，AREG、CEACAM5、FCRL1与NOTCH1，AREG、CEACAM5、FCRL1与PTX3，AREG、CEACAM5、FCRL1与SERPINA1，AREG、CEACAM5、FCRL1与TMPRSS15，AREG、CEACAM5、FCRL1与TNC，AREG、CEACAM5、GDF15与NOTCH1，AREG、CEACAM5、GDF15与PTX3，AREG、CEACAM5、GDF15与SERPINA1，AREG、CEACAM5、GDF15与TMPRSS15，AREG、CEACAM5、GDF15与TNC，AREG、CEACAM5、NOTCH1与PTX3，AREG、CEACAM5、NOTCH1与SERPINA1，AREG、CEACAM5、NOTCH1与TMPRSS15，AREG、CEACAM5、NOTCH1与TNC，AREG、CEACAM5、PTX3与SERPINA1，AREG、CEACAM5、PTX3与TMPRSS15，AREG、CEACAM5、PTX3与TNC，AREG、CEACAM5、SERPINA1与TMPRSS15，AREG、CEACAM5、SERPINA1与TNC，AREG、CEACAM5、TMPRSS15与TNC，AREG、COMP、EDA2R与FCRL1，AREG、COMP、EDA2R与GDF15，AREG、COMP、EDA2R与NOTCH1，AREG、COMP、EDA2R与PTX3，AREG、COMP、EDA2R与SERPINA1，AREG、COMP、EDA2R与TNC，AREG、COMP、FCRL1与GDF15，AREG、COMP、FCRL1与NOTCH1，AREG、COMP、FCRL1与PTX3，AREG、COMP、FCRL1与SERPINA1，AREG、COMP、FCRL1与TMPRSS15，AREG、COMP、FCRL1与TNC，AREG、COMP、GDF15与NOTCH1，AREG、COMP、GDF15与PTX3，AREG、COMP、GDF15与SERPINA1，AREG、COMP、GDF15与TMPRSS15，AREG、COMP、GDF15与TNC，AREG、COMP、NOTCH1与PTX3，AREG、COMP、NOTCH1与SERPINA1，AREG、COMP、NOTCH1与TMPRSS15，AREG、COMP、NOTCH1与TNC，AREG、COMP、PTX3与SERPINA1，AREG、COMP、PTX3与TMPRSS15，AREG、COMP、PTX3与TNC，AREG、COMP、SERPINA1与TMPRSS15，AREG、COMP、SERPINA1与TNC，AREG、COMP、TMPRSS15与TNC，AREG、EDA2R、FCRL1与GDF15，AREG、EDA2R、FCRL1与NOTCH1，AREG、EDA2R、FCRL1与PTX3，AREG、EDA2R、FCRL1与SERPINA1，AREG、EDA2R、FCRL1与TMPRSS15，AREG、EDA2R、FCRL1与TNC，AREG、EDA2R、GDF15与NOTCH1，AREG、EDA2R、GDF15与PTX3，AREG、EDA2R、GDF15与SERPINA1，AREG、EDA2R、GDF15与TMPRSS15，AREG、EDA2R、GDF15与TNC，AREG、EDA2R、NOTCH1与PTX3，AREG、EDA2R、NOTCH1与SERPINA1，AREG、EDA2R、NOTCH1与TMPRSS15，AREG、EDA2R、NOTCH1与TNC，AREG、EDA2R、PTX3与SERPINA1，AREG、EDA2R、PTX3与TMPRSS15，AREG、EDA2R、PTX3与TNC，AREG、EDA2R、SERPINA1与TMPRSS15，AREG、EDA2R、SERPINA1与TNC，AREG、EDA2R、TMPRSS15与TNC，AREG、FCRL1、GDF15与NOTCH1，AREG、FCRL1、GDF15与PTX3，AREG、FCRL1、GDF15与SERPINA1，AREG、FCRL1、GDF15与TMPRSS15，AREG、FCRL1、GDF15与TNC，AREG、FCRL1、NOTCH1与PTX3，AREG、FCRL1、NOTCH1与SERPINA1，AREG、FCRL1、NOTCH1与TMPRSS15，AREG、FCRL1、NOTCH1与TNC，AREG、FCRL1、PTX3与SERPINA1，AREG、FCRL1、PTX3与TMPRSS15，AREG、FCRL1、PTX3与TNC，AREG、FCRL1、SERPINA1与TMPRSS15，AREG、FCRL1、SERPINA1与TNC，AREG、FCRL1、TMPRSS15与TNC，AREG、GDF15、NOTCH1与PTX3，AREG、GDF15、NOTCH1与SERPINA1，AREG、GDF15、NOTCH1与TMPRSS15，AREG、GDF15、NOTCH1与TNC，AREG、GDF15、PTX3与SERPINA1，AREG、GDF15、PTX3与TMPRSS15，AREG、GDF15、PTX3与TNC，AREG、GDF15、SERPINA1与TMPRSS15，AREG、GDF15、SERPINA1与TNC，AREG、GDF15、TMPRSS15与TNC，AREG、NOTCH1、PTX3与SERPINA1，AREG、NOTCH1、PTX3与TMPRSS15，AREG、NOTCH1、PTX3与TNC，AREG、NOTCH1、SERPINA1与TMPRSS15，AREG、NOTCH1、SERPINA1与TNC，AREG、NOTCH1、TMPRSS15与TNC，AREG、PTX3、SERPINA1与TMPRSS15，AREG、PTX3、SERPINA1与TNC，AREG、PTX3、TMPRSS15与TNC，AREG、SERPINA1、TMPRSS15与TNC，CEACAM5、COMP、EDA2R与FCRL1，CEACAM5、COMP、EDA2R与GDF15，CEACAM5、COMP、EDA2R与NOTCH1，CEACAM5、COMP、EDA2R与PTX3，CEACAM5、COMP、EDA2R与SERPINA1，CEACAM5、COMP、EDA2R与TMPRSS15，CEACAM5、COMP、EDA2R与TNC，CEACAM5、COMP、FCRL1与GDF15，CEACAM5、COMP、FCRL1与NOTCH1，CEACAM5、COMP、FCRL1与PTX3，CEACAM5、COMP、FCRL1与SERPINA1，CEACAM5、COMP、FCRL1与TMPRSS15，CEACAM5、COMP、FCRL1与TNC，CEACAM5、COMP、GDF15与NOTCH1，CEACAM5、COMP、GDF15与SERPINA1，CEACAM5、COMP、GDF15与TMPRSS15，CEACAM5、COMP、NOTCH1与PTX3，CEACAM5、COMP、NOTCH1与SERPINA1，CEACAM5、COMP、NOTCH1与TMPRSS15，CEACAM5、COMP、NOTCH1与TNC，CEACAM5、COMP、PTX3与SERPINA1，CEACAM5、COMP、PTX3与TMPRSS15，CEACAM5、COMP、PTX3与TNC，CEACAM5、COMP、SERPINA1与TMPRSS15，CEACAM5、COMP、SERPINA1与TNC，CEACAM5、COMP、TMPRSS15与TNC，CEACAM5、EDA2R、FCRL1与GDF15，CEACAM5、EDA2R、FCRL1与NOTCH1，CEACAM5、EDA2R、FCRL1与PTX3，CEACAM5、EDA2R、FCRL1与SERPINA1，CEACAM5、EDA2R、FCRL1与TMPRSS15，CEACAM5、EDA2R、FCRL1与TNC，CEACAM5、EDA2R、GDF15与NOTCH1，CEACAM5、EDA2R、GDF15与PTX3，CEACAM5、EDA2R、GDF15与SERPINA1，CEACAM5、EDA2R、GDF15与TMPRSS15，CEACAM5、EDA2R、GDF15与TNC，CEACAM5、EDA2R、NOTCH1与PTX3，CEACAM5、EDA2R、NOTCH1与SERPINA1，CEACAM5、EDA2R、NOTCH1与TMPRSS15，CEACAM5、EDA2R、NOTCH1与TNC，CEACAM5、EDA2R、PTX3与SERPINA1，CEACAM5、EDA2R、PTX3与TMPRSS15，CEACAM5、EDA2R、PTX3与TNC，CEACAM5、EDA2R、SERPINA1与TMPRSS15，CEACAM5、EDA2R、SERPINA1与TNC，CEACAM5、EDA2R、TMPRSS15与TNC，CEACAM5、FCRL1、GDF15与NOTCH1，CEACAM5、FCRL1、GDF15与PTX3，CEACAM5、FCRL1、GDF15与SERPINA1，CEACAM5、FCRL1、GDF15与TMPRSS15，CEACAM5、FCRL1、GDF15与TNC，CEACAM5、FCRL1、NOTCH1与PTX3，CEACAM5、FCRL1、NOTCH1与SERPINA1，CEACAM5、FCRL1、NOTCH1与TMPRSS15，CEACAM5、FCRL1、NOTCH1与TNC，CEACAM5、FCRL1、PTX3与SERPINA1，CEACAM5、FCRL1、PTX3与TMPRSS15，CEACAM5、FCRL1、PTX3与TNC，CEACAM5、FCRL1、SERPINA1与TMPRSS15，CEACAM5、FCRL1、SERPINA1与TNC，CEACAM5、FCRL1、TMPRSS15与TNC，CEACAM5、GDF15、NOTCH1与SERPINA1，CEACAM5、GDF15、NOTCH1与TMPRSS15，CEACAM5、GDF15、NOTCH1与TNC，CEACAM5、GDF15、PTX3与SERPINA1，CEACAM5、GDF15、PTX3与TMPRSS15，CEACAM5、GDF15、PTX3与TNC，CEACAM5、GDF15、SERPINA1与TMPRSS15，CEACAM5、GDF15、SERPINA1与TNC，CEACAM5、GDF15、TMPRSS15与TNC，CEACAM5、NOTCH1、PTX3与SERPINA1，CEACAM5、NOTCH1、PTX3与TMPRSS15，CEACAM5、NOTCH1、PTX3与TNC，CEACAM5、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、NOTCH1、SERPINA1与TNC，CEACAM5、NOTCH1、TMPRSS15与TNC，CEACAM5、PTX3、SERPINA1与TMPRSS15，CEACAM5、PTX3、SERPINA1与TNC，CEACAM5、PTX3、TMPRSS15与TNC，CEACAM5、SERPINA1、TMPRSS15与TNC，COMP、EDA2R、FCRL1与GDF15，COMP、EDA2R、FCRL1与NOTCH1，COMP、EDA2R、FCRL1与PTX3，COMP、EDA2R、FCRL1与SERPINA1，COMP、EDA2R、FCRL1与TMPRSS15，COMP、EDA2R、FCRL1与TNC，COMP、EDA2R、GDF15与NOTCH1，COMP、EDA2R、GDF15与PTX3，COMP、EDA2R、GDF15与SERPINA1，COMP、EDA2R、GDF15与TMPRSS15，COMP、EDA2R、GDF15与TNC，COMP、EDA2R、NOTCH1与PTX3，COMP、EDA2R、NOTCH1与SERPINA1，COMP、EDA2R、NOTCH1与TMPRSS15，COMP、EDA2R、NOTCH1与TNC，COMP、EDA2R、PTX3与SERPINA1，COMP、EDA2R、PTX3与TNC，COMP、EDA2R、SERPINA1与TMPRSS15，COMP、EDA2R、SERPINA1与TNC，COMP、EDA2R、TMPRSS15与TNC，COMP、FCRL1、GDF15与SERPINA1，COMP、FCRL1、GDF15与TNC，COMP、FCRL1、NOTCH1与PTX3，COMP、FCRL1、NOTCH1与SERPINA1，COMP、FCRL1、NOTCH1与TMPRSS15，COMP、FCRL1、NOTCH1与TNC，COMP、FCRL1、PTX3与SERPINA1，COMP、FCRL1、PTX3与TMPRSS15，COMP、FCRL1、PTX3与TNC，COMP、FCRL1、SERPINA1与TMPRSS15，COMP、FCRL1、SERPINA1与TNC，COMP、FCRL1、TMPRSS15与TNC，COMP、GDF15、NOTCH1与TMPRSS15，COMP、GDF15、NOTCH1与TNC，COMP、GDF15、PTX3与SERPINA1，COMP、GDF15、SERPINA1与TMPRSS15，COMP、GDF15、SERPINA1与TNC，COMP、NOTCH1、PTX3与SERPINA1，COMP、NOTCH1、PTX3与TMPRSS15，COMP、NOTCH1、PTX3与TNC，COMP、NOTCH1、SERPINA1与TMPRSS15，COMP、NOTCH1、SERPINA1与TNC，COMP、NOTCH1、TMPRSS15与TNC，COMP、PTX3、SERPINA1与TMPRSS15，COMP、PTX3、SERPINA1与TNC，COMP、PTX3、TMPRSS15与TNC，COMP、SERPINA1、TMPRSS15与TNC，EDA2R、FCRL1、GDF15与NOTCH1，EDA2R、FCRL1、GDF15与PTX3，EDA2R、FCRL1、GDF15与SERPINA1，EDA2R、FCRL1、GDF15与TMPRSS15，EDA2R、FCRL1、GDF15与TNC，EDA2R、FCRL1、NOTCH1与PTX3，EDA2R、FCRL1、NOTCH1与SERPINA1，EDA2R、FCRL1、NOTCH1与TMPRSS15，EDA2R、FCRL1、NOTCH1与TNC，EDA2R、FCRL1、PTX3与SERPINA1，EDA2R、FCRL1、PTX3与TMPRSS15，EDA2R、FCRL1、PTX3与TNC，EDA2R、FCRL1、SERPINA1与TMPRSS15，EDA2R、FCRL1、SERPINA1与TNC，EDA2R、FCRL1、TMPRSS15与TNC，EDA2R、GDF15、NOTCH1与PTX3，EDA2R、GDF15、NOTCH1与SERPINA1，EDA2R、GDF15、NOTCH1与TMPRSS15，EDA2R、GDF15、NOTCH1与TNC，EDA2R、GDF15、PTX3与SERPINA1，EDA2R、GDF15、PTX3与TMPRSS15，EDA2R、GDF15、PTX3与TNC，EDA2R、GDF15、SERPINA1与TMPRSS15，EDA2R、GDF15、SERPINA1与TNC，EDA2R、GDF15、TMPRSS15与TNC，EDA2R、NOTCH1、PTX3与SERPINA1，EDA2R、NOTCH1、PTX3与TMPRSS15，EDA2R、NOTCH1、PTX3与TNC，EDA2R、NOTCH1、SERPINA1与TMPRSS15，EDA2R、NOTCH1、SERPINA1与TNC，EDA2R、NOTCH1、TMPRSS15与TNC，EDA2R、PTX3、SERPINA1与TMPRSS15，EDA2R、PTX3、SERPINA1与TNC，EDA2R、PTX3、TMPRSS15与TNC，EDA2R、SERPINA1、TMPRSS15与TNC，FCRL1、GDF15、NOTCH1与SERPINA1，FCRL1、GDF15、NOTCH1与TMPRSS15，FCRL1、GDF15、NOTCH1与TNC，FCRL1、GDF15、PTX3与SERPINA1，FCRL1、GDF15、PTX3与TMPRSS15，FCRL1、GDF15、PTX3与TNC，FCRL1、GDF15、SERPINA1与TMPRSS15，FCRL1、GDF15、SERPINA1与TNC，FCRL1、GDF15、TMPRSS15与TNC，FCRL1、NOTCH1、PTX3与SERPINA1，FCRL1、NOTCH1、PTX3与TMPRSS15，FCRL1、NOTCH1、PTX3与TNC，FCRL1、NOTCH1、SERPINA1与TMPRSS15，FCRL1、NOTCH1、SERPINA1与TNC，FCRL1、NOTCH1、TMPRSS15与TNC，FCRL1、PTX3、SERPINA1与TMPRSS15，FCRL1、PTX3、SERPINA1与TNC，FCRL1、PTX3、TMPRSS15与TNC，FCRL1、SERPINA1、TMPRSS15与TNC，GDF15、NOTCH1、PTX3与SERPINA1，GDF15、NOTCH1、PTX3与TNC，GDF15、NOTCH1、SERPINA1与TMPRSS15，GDF15、NOTCH1、SERPINA1与TNC，GDF15、NOTCH1、TMPRSS15与TNC，GDF15、PTX3、SERPINA1与TMPRSS15，GDF15、PTX3、SERPINA1与TNC，GDF15、PTX3、TMPRSS15与TNC，GDF15、SERPINA1、TMPRSS15与TNC，NOTCH1、PTX3、SERPINA1与TMPRSS15，NOTCH1、PTX3、SERPINA1与TNC，NOTCH1、PTX3、TMPRSS15与TNC，NOTCH1、SERPINA1、TMPRSS15与TNC，或PTX3、SERPINA1、TMPRSS15与TNC。Preferably, the 4 markers combination is: NOTCH1, COMP, GDF15 and PTX3, CEACAM5, COMP, GDF15 and PTX3, TMPRSS15, PTX3, GDF15 and COMP, CEACAM5, GDF15, NOTCH1 and PTX3, AREG, COMP, EDA2R and TMPRSS15, COMP, FCRL1, GDF15 and NOTCH1, COMP, GDF15, PTX3 and TNC, COMP, FCRL1, GDF15 and TMPRSS15, GDF15, NOTCH1, PTX3 and TMPRSS15, CEACAM5, COMP, GDF15 and TNC, CO MP, EDA2R, PTX3 and TMPRSS15, COMP, FCRL1, GDF15 and PTX3, FCRL1, GDF15, NOTCH1 and PTX3, COMP, GDF15, NOTCH1 and SERPINA1, COMP, GDF15, TMPRSS15 and TNC, AREG, CEACAM5, COMP and EDA2R, AREG, CEACAM5, COMP and FCRL1, AREG, CEACAM5, COMP and GDF15, AREG, CEACAM5, COMP and NOTCH1, AREG, CEACAM5, COMP and PTX3, AREG, CEACAM5, COMP and SERPI NA1, AREG, CEACAM5, COMP and TMPRSS15, AREG, CEACAM5, COMP and TNC, AREG, CEACAM5, EDA2R and FCRL1, AREG, CEACAM5, EDA2R and GDF15, AREG, CEACAM5, EDA2R and NOTCH1, AREG, CEACAM5, EDA2R and PTX3, AREG, CEACAM5, EDA2R and SERPINA1, AREG, CEACAM5, EDA2R and TMPRSS15, AREG, CEACAM5, EDA2R and TNC, AREG, CEACAM5, FCRL1 and GDF15, AREG, CEACAM5 EACAM5, FCRL1 and NOTCH1, AREG, CEACAM5, FCRL1 and PTX3, AREG, CEACAM5, FCRL1 and SERPINA1, AREG, CEACAM5, FCRL1 and TMPRSS15, AREG, CEACAM5, FCRL1 and TNC, AREG, CEACAM5, GDF15 and NOTCH1, AREG, CEACAM5, GDF15 and PTX3, AREG, CEACAM5, GDF15 and SERPINA1, AREG, CEACAM5, GDF15 and TMPRSS15, AREG, CEACAM5, GDF15 and TNC, AREG, CEACAM 5. NOTCH1 and PTX3, AREG, CEACAM5, NOTCH1 and SERPINA1, AREG, CEACAM5, NOTCH1 and TMPRSS15, AREG, CEACAM5, NOTCH1 and TNC, AREG, CEACAM5, PTX3 and SERPINA1, AREG, CEACAM5, PTX3 and TMPRSS15, AREG, CEACAM5, PTX3 and TNC, AREG, CEACAM5, SERPINA1 and TMPRSS15, AREG, CEACAM5, SERPINA1 and TNC, AREG, CEACAM5, TMPRSS15 and TNC, AREG, COM P, EDA2R and FCRL1, AREG, COMP, EDA2R and GDF15, AREG, COMP, EDA2R and NOTCH1, AREG, COMP, EDA2R and PTX3, AREG, COMP, EDA2R and SERPINA1, AREG, COMP, EDA2R and TNC, AREG, COMP, FCRL1 and GDF15, AREG, COMP, FCRL1 and NOTCH1, AREG, COMP, FCRL1 and PTX3, AREG, COMP, FCRL1 and SERPINA1, AREG, COMP, FCRL1 and TMPRSS15, AREG, COMP, FCRL1 and TNC, AR EG, COMP, GDF15 and NOTCH1, AREG, COMP, GDF15 and PTX3, AREG, COMP, GDF15 and SERPINA1, AREG, COMP, GDF15 and TMPRSS15, AREG, COMP, GDF15 and TNC, AREG, COMP, NOTCH1 and PTX3, AREG, COMP, NOTCH1 and SERPINA1, AREG, COMP, NOTCH1 and TMPRSS15, AREG, COMP, NOTCH1 and TNC, AREG, COMP, PTX3 and SERPINA1, AREG, COMP, PTX3 and TMPRSS15, AREG, COMP P, PTX3 and TNC, AREG, COMP, SERPINA1 and TMPRSS15, AREG, COMP, SERPINA1 and TNC, AREG, COMP, TMPRSS15 and TNC, AREG, EDA2R, FCRL1 and GDF15, AREG, EDA2R, FCRL1 and NOTCH1, AREG, EDA2R, FCRL1 and PTX3, AREG, EDA2R, FCRL1 and SERPINA1, AREG, EDA2R, FCRL1 and TMPRSS15, AREG, EDA2R, FCRL1 and TNC, AREG, EDA2R, GDF15 and NOTCH1, AREG, EDA2R, G DF15 and PTX3, AREG, EDA2R, GDF15 and SERPINA1, AREG, EDA2R, GDF15 and TMPRSS15, AREG, EDA2R, GDF15 and TNC, AREG, EDA2R, NOTCH1 and PTX3, AREG, EDA2R, NOTCH1 and SERPINA1, AREG, EDA2R, NOTCH1 and TMPRSS15, AREG, EDA2R, NOTCH1 and TNC, AREG, EDA2R, PTX3 and SERPINA1, AREG, EDA2R, PTX3 and TMPRSS15, AREG, EDA2R, PTX3 and TNC, AREG, EDA2R, SERPINA1 and TMPRSS15, AREG, EDA2R, SERPINA1 and TNC, AREG, EDA2R, TMPRSS15 and TNC, AREG, FCRL1, GDF15 and NOTCH1, AREG, FCRL1, GDF15 and PTX3, AREG, FCRL1, GDF15 and SERPINA1, AREG, FCRL1, GDF15 and TMPRSS15, AREG, FCRL1, GDF15 and TNC, AREG, FCRL1, NOTCH1 and PTX3, AREG, FCRL1, NOTCH1 and SERPINA1, AREG, FCRL1, NOTCH1 and TMPRSS15, A REG, FCRL1, NOTCH1, and TNC, AREG, FCRL1, PTX3, and SERPINA1, AREG, FCRL1, PTX3, and TMPRSS15, AREG, FCRL1, PTX3, and TNC, AREG, FCRL1, SERPINA1, and TMPRSS15, AREG, FCRL1, SERPINA1, and TNC, AREG, FCRL1, TMPRSS15, and TNC, AREG, GDF15, NOTCH1, and PTX3, AREG, GDF15, NOTCH1, and SERPINA1, AREG, GDF15, NOTCH1, and TMPRSS15, AREG, GDF15, NOTCH1, and TNC, AREG, GDF15, PTX3, and SERPINA1, AREG, GDF15, PTX3, and TMPRSS15, AREG, GDF15, PTX3, and TNC, AREG, GDF15, SERPINA1, and TMPRSS15, AREG, GDF15, SERPINA1, and TNC, AREG, GDF15, TMPRSS15, and TNC, AREG, NOTCH1, PTX3, and SERPINA1, AREG, NOTCH1, PTX3, and TMPRSS15, AREG, NOTCH1, PTX3, and TNC, AREG, NOTCH1, SERPINA1, and TMPRSS15, AREG, NOTCH1, PTX3, and TNC. H1, SERPINA1 and TNC, AREG, NOTCH1, TMPRSS15 and TNC, AREG, PTX3, SERPINA1 and TMPRSS15, AREG, PTX3, SERPINA1 and TNC, AREG, PTX3, TMPRSS15 and TNC, AREG, SERPINA1, TMPRSS15 and TNC, CEACAM5, COMP, EDA2R and FCRL1, CEACAM5, COMP, EDA2R and GDF15, CEACAM5, COMP, EDA2R and NOTCH1, CEACAM5, COMP, EDA2R and PTX3, CEACAM5, COMP, EDA2R and SE RPINA1, CEACAM5, COMP, EDA2R and TMPRSS15, CEACAM5, COMP, EDA2R and TNC, CEACAM5, COMP, FCRL1 and GDF15, CEACAM5, COMP, FCRL1 and NOTCH1, CEACAM5, COMP, FCRL1 and PTX3, CEACAM5, COMP, FCRL1 and SERPINA1, CEACAM5, COMP, FCRL1 and TMPRSS15, CEACAM5, COMP, FCRL1 and TNC, CEACAM5, COMP, GDF15 and NOTCH1, CEACAM5, COMP, GDF15 and SERPIN A1, CEACAM5, COMP, GDF15 and TMPRSS15, CEACAM5, COMP, NOTCH1 and PTX3, CEACAM5, COMP, NOTCH1 and SERPINA1, CEACAM5, COMP, NOTCH1 and TMPRSS15, CEACAM5, COMP, NOTCH1 and TNC, CEACAM5, COMP, PTX3 and SERPINA1, CEACAM5, COMP, PTX3 and TMPRSS15, CEACAM5, COMP, PTX3 and TNC, CEACAM5, COMP, SERPINA1 and TMPRSS15, CEACAM5, COMP, SERPI NA1 and TNC, CEACAM5, COMP, TMPRSS15 and TNC, CEACAM5, EDA2R, FCRL1 and GDF15, CEACAM5, EDA2R, FCRL1 and NOTCH1, CEACAM5, EDA2R, FCRL1 and PTX3, CEACAM5, EDA2R, FCRL1 and SERPINA1, CEACAM5, EDA2R, FCRL1 and TMPRSS15, CEACAM5, EDA2R, FCRL1 and TNC, CEACAM5, EDA2R, GDF15 and NOTCH1, CEACAM5, EDA2R, GDF15 and PTX3, CEACAM5, EDA2R, GDF1 5 and SERPINA1, CEACAM5, EDA2R, GDF15 and TMPRSS15, CEACAM5, EDA2R, GDF15 and TNC, CEACAM5, EDA2R, NOTCH1 and PTX3, CEACAM5, EDA2R, NOTCH1 and SERPINA1, CEACAM5, EDA2R, NOTCH1 and TMPRSS15, CEACAM5, EDA2R, NOTCH1 and TNC, CEACAM5, EDA2R, PTX3 and SERPINA1, CEACAM5, EDA2R, PTX3 and TMPRSS15, CEACAM5, EDA2R, PTX3 and TNC, CEACAM5, E DA2R, SERPINA1 and TMPRSS15, CEACAM5, EDA2R, SERPINA1 and TNC, CEACAM5, EDA2R, TMPRSS15 and TNC, CEACAM5, FCRL1, GDF15 and NOTCH1, CEACAM5, FCRL1, GDF15 and PTX3, CEACAM5, FCRL1, GDF15 and SERPINA1, CEACAM5, FCRL1, GDF15 and TMPRSS15, CEACAM5, FCRL1, GDF15 and TNC, CEACAM5, FCRL1, NOTCH1 and PTX3, CEACAM5, FCRL1, NOTCH1 and SERPI NA1, CEACAM5, FCRL1, NOTCH1 and TMPRSS15, CEACAM5, FCRL1, NOTCH1 and TNC, CEACAM5, FCRL1, PTX3 and SERPINA1, CEACAM5, FCRL1, PTX3 and TMPRSS15, CEACAM5, FCRL1, PTX3 and TNC, CEACAM5, FCRL1, SERPINA1 and TMPRSS15, CEACAM5, FCRL1, SERPINA1 and TNC, CEACAM5, FCRL1, TMPRSS15 and TNC, CEACAM5, GDF15, NOTCH1 and SERPINA1, CEACAM5, G DF15, NOTCH1 and TMPRSS15, CEACAM5, GDF15, NOTCH1 and TNC, CEACAM5, GDF15, PTX3 and SERPINA1, CEACAM5, GDF15, PTX3 and TMPRSS15, CEACAM5, GDF15, PTX3 and TNC, CEACAM5, GDF15, SERPINA1 and TMPRSS15, CEACAM5, GDF15, SERPINA1 and TNC, CEACAM5, GDF15, TMPRSS15 and TNC, CEACAM5, NOTCH1, PTX3 and SERPINA1, CEACAM5, NOTCH1, PTX3 and TMP RSS15, CEACAM5, NOTCH1, PTX3 and TNC, CEACAM5, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, NOTCH1, SERPINA1 and TNC, CEACAM5, NOTCH1, TMPRSS15 and TNC, CEACAM5, PTX3, SERPINA1 and TMPRSS15, CEACAM5, PTX3, SERPINA1 and TNC, CEACAM5, PTX3, TMPRSS15 and TNC, CEACAM5, SERPINA1, TMPRSS15 and TNC, COMP, EDA2R, FCRL1 and GDF15, COMP, EDA 2R, FCRL1 and NOTCH1, COMP, EDA2R, FCRL1 and PTX3, COMP, EDA2R, FCRL1 and SERPINA1, COMP, EDA2R, FCRL1 and TMPRSS15, COMP, EDA2R, FCRL1 and TNC, COMP, EDA2R, GDF15 and NOTCH1, COMP, EDA2R, GDF15 and PTX3, COMP, EDA2R, GDF15 and SERPINA1, COMP, EDA2R, GDF15 and TMPRSS15, COMP, EDA2R, GDF15 and TNC, COMP, EDA2R, NOTCH1 and PTX3, COMP, EDA2R 、NOTCH1与SERPINA1，COMP、EDA2R、NOTCH1与TMPRSS15，COMP、EDA2R、NOTCH1与TNC，COMP、EDA2R、PTX3与SERPINA1，COMP、EDA2R、PTX3与TNC，COMP、EDA2R、SERPINA1与TMPRSS15，COMP、EDA2R、SERPINA1与TNC，COMP、EDA2R、TMPRSS15与TNC，COMP、FCRL1、GDF15与SERPINA1，COMP、FCRL1、GDF15与TNC，COMP、FCRL1、NOTCH1与PTX3，COMP、 FCRL1, NOTCH1, and SERPINA1, COMP, FCRL1, NOTCH1, and TMPRSS15, COMP, FCRL1, NOTCH1, and TNC, COMP, FCRL1, PTX3, and SERPINA1, COMP, FCRL1, PTX3, and TMPRSS15, COMP, FCRL1, PTX3, and TNC, COMP, FCRL1, SERPINA1, and TMPRSS15, COMP, FCRL1, SERPINA1, and TNC, COMP, FCRL1, TMPRSS15, and TNC, COMP, GDF15, NOTCH1, and TMPRSS15, COMP, GDF15, NOTCH1, and T NC, COMP, GDF15, PTX3 and SERPINA1, COMP, GDF15, SERPINA1 and TMPRSS15, COMP, GDF15, SERPINA1 and TNC, COMP, NOTCH1, PTX3 and SERPINA1, COMP, NOTCH1, PTX3 and TMPRSS15, COMP, NOTCH1, PTX3 and TNC, COMP, NOTCH1, SERPINA1 and TMPRSS15, COMP, NOTCH1, SERPINA1 and TNC, COMP, NOTCH1, TMPRSS15 and TNC, COMP, PTX3, SERPINA1 and TMPRSS15, C OMP, PTX3, SERPINA1 and TNC, COMP, PTX3, TMPRSS15 and TNC, COMP, SERPINA1, TMPRSS15 and TNC, EDA2R, FCRL1, GDF15 and NOTCH1, EDA2R, FCRL1, GDF15 and PTX3, EDA2R, FCRL1, GDF15 and SERPINA1, EDA2R, FCRL1, GDF15 and TMPRSS15, EDA2R, FCRL1, GDF15 and TNC, EDA2R, FCRL1, NOTCH1 and PTX3, EDA2R, FCRL1, NOTCH1 and SERPINA1, EDA2R, FCRL1, NOT CH1 and TMPRSS15, EDA2R, FCRL1, NOTCH1 and TNC, EDA2R, FCRL1, PTX3 and SERPINA1, EDA2R, FCRL1, PTX3 and TMPRSS15, EDA2R, FCRL1, PTX3 and TNC, EDA2R, FCRL1, SERPINA1 and TMPRSS15, EDA2R, FCRL1, SERPINA1 and TNC, EDA2R, FCRL1, TMPRSS15 and TNC, EDA2R, GDF15, NOTCH1 and PTX3, EDA2R, GDF15, NOTCH1 and SERPINA1, EDA2R, GDF15, NOTCH1 and TMP RSS15, EDA2R, GDF15, NOTCH1 and TNC, EDA2R, GDF15, PTX3 and SERPINA1, EDA2R, GDF15, PTX3 and TMPRSS15, EDA2R, GDF15, PTX3 and TNC, EDA2R, GDF15, SERPINA1 and TMPRSS15, EDA2R, GDF15, SERPINA1 and TNC, EDA2R, GDF15, TMPRSS15 and TNC, EDA2R, NOTCH1, PTX3 and SERPINA1, EDA2R, NOTCH1, PTX3 and TMPRSS15, EDA2R, NOTCH1, PTX3 and TNC, EDA2R 、NOTCH1、SERPINA1与TMPRSS15，EDA2R、NOTCH1、SERPINA1与TNC，EDA2R、NOTCH1、TMPRSS15与TNC，EDA2R、PTX3、SERPINA1与TMPRSS15，EDA2R、PTX3、SERPINA1与TNC，EDA2R、PTX3、TMPRSS15与TNC，EDA2R、SERPINA1、TMPRSS15与TNC，FCRL1、GDF15、NOTCH1与SERPINA1，FCRL1、GDF15、NOTCH1与TMPRSS15，FCRL1、GDF15、NOTCH1与TNC，F CRL1, GDF15, PTX3 and SERPINA1, FCRL1, GDF15, PTX3 and TMPRSS15, FCRL1, GDF15, PTX3 and TNC, FCRL1, GDF15, SERPINA1 and TMPRSS15, FCRL1, GDF15, SERPINA1 and TNC, FCRL1, GDF15, SERPINA1 and TNC, FCRL1, GDF15, TMPRSS15 and TNC, FCRL1, NOTCH1, PTX3 and SERPINA1, FCRL1, NOTCH1, PTX3 and TMPRSS15, FCRL1, NOTCH1, PTX3 and TNC, FCRL1, NOTCH1, SERPINA1 and TMPRSS15, FCRL 1. NOTCH1, SERPINA1 and TNC, FCRL1, NOTCH1, TMPRSS15 and TNC, FCRL1, PTX3, SERPINA1 and TMPRSS15, FCRL1, PTX3, SERPINA1 and TNC, FCRL1, PTX3, TMPRSS15 and TNC, FCRL1, SERPINA1, TMPRSS15 and TNC, GDF15, NOTCH1, PTX3 and SERPINA1, GDF15, NOTCH1, PTX3 and TNC, GDF15, NOTCH1, SERPINA1 and TMPRSS15, GDF15, NOTCH1, SERPINA1 and TNC, GDF1 5. NOTCH1, TMPRSS15 and TNC, GDF15, PTX3, SERPINA1 and TMPRSS15, GDF15, PTX3, SERPINA1 and TNC, GDF15, PTX3, TMPRSS15 and TNC, GDF15, SERPINA1, TMPRSS15 and TNC, NOTCH1, PTX3, SERPINA1 and TMPRSS15, NOTCH1, PTX3, SERPINA1 and TNC, NOTCH1, PTX3, TMPRSS15 and TNC, NOTCH1, SERPINA1, TMPRSS15 and TNC, or PTX3, SERPINA1, TMPRSS15 and TNC.
优选地，所述A包含5markers组合，所述5markers组合为所述B中的任意五种。Preferably, A comprises a combination of 5 markers, and the combination of 5 markers is any five of the combinations in B.
优选地，所述5markers组合为c1)和c2):Preferably, the 5 markers are combined into c1) and c2):
c1)所述4markers组合(优选上述332个4markers组合中的任一种)；c1) the 4-markers combination (preferably any one of the 332 4-markers combinations mentioned above);
c2)所述B中的任意一种；c2) any one of the above B;
所述c2)不同于c1)中所述4markers组合中的任意一个marker。The c2) is different from any marker in the combination of 4 markers in c1).
优选地，所述5markers组合为：TMPRSS15、SPP1、SOD3、MMP12与ADGRE1，SPP1、COMP、LMNB2、SOD3与SELL，PTX3、POF1B、THBS4、FASLG与TNC，NOTCH1、COMP、GDF15、PTX3与FAP，ADGRE1、GDF15、PTX3、THBS4与IGDCC4，SPP1、COMP、TNFRSF10B、ADGRE5与PROK1，SPP1、COMP、LMNB2、FCRL1与PKD1，PTX3、GDF15、RET、ADGRG2与CD48，TMPRSS15、PTX3、SPP1、THBS4与PROK1，SPP1、FCRL1、SOD3、ADGRE5与ITM2A，NOTCH3、ESM1、PLXDC2、LMNB2与MEGF9，PTX3、HMCN2、POF1B、FASLG与CDH23，PTX3、COMP、POF1B、FASLG与LMNB2，DCC、COMP、SPP1、PROK1与SOD3，TMPRSS15、SPP1、FCRL1、SOD3与NOS2，PTX3、POF1B、THBS4、EXTL1与SPP1，SPP1、LMNB2、FCRL1、SOD3与THBS4，COMP、GDF15、NOTCH1、PTX3与TMPRSS15，TMPRSS15、PTX3、GDF15、THBS4与LPL，NOTCH1、COMP、GDF15、PTX3与ADAMTS8，SPP1、LMNB2、SOD3、ADGRE5与BAG3，SPP1、COMP、FCRL1、SOD3与PGA4，TMPRSS15、SPP1、FCRL1、SOD3与ADGRE5，ADGRE2、SOD3、SPP1、LMNB2与CLEC3B，PTX3、ITGA11、POF1B、THBS4与ENPP6，NOTCH1、SPP1、TNFRSF10B、COMP与TCL1A，TMPRSS15、SPP1、FCRL1、SOD3与PROK1，SPP1、ENPP6、FCRL1、ADGRE5与THBS4，TMPRSS15、PTX3、GDF15、THBS4与FCER2，PTX3、GDF15、PLXDC2、THBS4与ADGRE2，GNAS、LMNB2、PLXDC2、PROK1与KRT19，PTX3、GDF15、COMP、ADGRG2与DCC，TMPRSS15、PTX3、SPP1、THBS4与IL6，PTX3、GDF15、THBS4、ADGRG2与FCER2，PTX3、GDF15、PLXDC2、THBS4与TCL1A，TMPRSS15、PTX3、SPP1、THBS4与FGF21，GDF15、SPP1、PLXDC2、COMP与PROK1，SPP1、COMP、FCRL1、IL4R与PLXDC2，PTX3、GDF15、RET、ADGRG2与TCL1A，PTX3、HMCN2、POF1B、FASLG与THBS4，PTX3、GDF15、THBS4、ADGRG2与BAG3，SPP1、COMP、LMNB2、FCRL1与ITM2A，ADGRE1、KRT19、LMNB2、COMP与TMPRSS15，DCC、COMP、SPP1、PROK1与ADAMTS8，PTX3、GDF15、POF1B、THBS4与CFP，ADGRE1、GDF15、PTX3、THBS4与DLK1，SPP1、LMNB2、SOD3、ADGRE5与COMP，TMPRSS15、COMP、PTX3、PGA4与DCC，GNAS、LMNB2、PLXDC2、PROK1与IL4R，SPP1、LMNB2、FCRL1、SOD3与CFP，SPP1、LMNB2、FCRL1、SOD3与AREG，PTX3、SPP1、COMP、FCRL1与LMNB2，TMPRSS15、SPP1、FCRL1、SOD3与CDH23，TMPRSS15、PTX3、GDF15、THBS4与AREG，SPP1、COMP、LMNB2、FCRL1与CNTN4，TMPRSS15、SPP1、COMP、FCRL1与PTPRS，PTX3、POF1B、THBS4、EXTL1与BMP4，SPP1、LMNB2、FCRL1、SOD3与PROK1，TMPRSS15、PTX3、GDF15、THBS4与IL6，SPP1、ADGRG2、FCRL1、SOD3与BAG3，PTX3、GDF15、COMP、RET与ADGRE1，SPP1、COMP、FCRL1、SOD3与PLXDC2，GNAS、LMNB2、PLXDC2、PROK1与LPL，SPP1、COMP、FCRL1、SOD3与NOS2，TMPRSS15、COMP、PTX3、PGA4与SOD3，TMPRSS15、PTX3、GDF15、THBS4与LBP，PTX3、GDF15、RET、ADGRG2与ITGA11，SPP1、ENPP6、FCRL1、ADGRE5与AREG，SPP1、PLXDC2、FCRL1、SOD3与ITGA11，TMPRSS15、SPP1、FCRL1、SOD3与THBS4，ADGRE2、SOD3、SPP1、LMNB2与ITGA11，SPP1、COMP、FCRL1、SOD3与C9，PTX3、GDF15、THBS4、ADGRE5与CEACAM16，PTX3、GDF15、RET、ADGRG2与FASLG，PTX3、POF1B、THBS4、FASLG与TMPRSS15，PTX3、COMP、POF1B、FCRL1与GDF15，TMPRSS15、PTX3、GDF15、COMP与RET，AREG、CEACAM5、SOD3、RET与CFP，SPP1、PLXDC2、COMP、LMNB2与GCG，ADGRE1、GDF15、PTX3、THBS4与CEACAM5，PTX3、GDF15、COMP、ADGRG2与FASLG，TMPRSS15、COMP、PTX3、PGA4与FCRL1，PTX3、GDF15、COMP、FASLG与TMPRSS15，TMPRSS15、SPP1、COMP、FCRL1与CCL7，PTX3、GDF15、THBS4、CLEC3B与TMPRSS15，PTX3、SPP1、COMP、CNTN4与TNC，SPP1、COMP、FCRL1、ADGRE5与PROK1，SPP1、COMP、TNFRSF10B、ADGRE5与SERPINA1，TMPRSS15、SPP1、COMP、FCRL1与PGA4，TMPRSS15、COMP、PTX3、PGA4与IL6，SPP1、FCRL1、SOD3、ADGRE5与NOS2，TMPRSS15、SPP1、COMP、IL4R与FCRL1，PTX3、COMP、POF1B、FCRL1与LMNB2，TMPRSS15、PTX3、GDF15、THBS4与MEGF9，SPP1、COMP、LMNB2、FCRL1与EDA2R，SPP1、COMP、LMNB2、FCRL1与GRK5，TMPRSS15、SPP1、COMP、CLEC3B与PGA4，NOTCH1、COMP、GDF15、PTX3与SPP1，SPP1、COMP、LMNB2、FCRL1与ITGB7，ADGRE1、GDF15、PTX3、THBS4与FGF21，ADGRE1、KRT19、LMNB2、COMP与TCL1A，SPP1、COMP、LMNB2、FCRL1与ITGB1，TMPRSS15、PTX3、GDF15、THBS4与PLXDC2，PTX3、POF1B、THBS4、EXTL1与RET，GNAS、LMNB2、PLXDC2、PROK1与CNTN4，SPP1、PLXDC2、COMP、IL4R与TNC，PTX3、GDF15、COMP、POF1B与PGA4，SPP1、COMP、LMNB2、FCRL1与GSN，TMPRSS15、PTX3、SPP1、THBS4与PGA4，SPP1、COMP、LMNB2、FCRL1与BAG3，NOTCH1、COMP、GDF15、PTX3与KRT19，ADGRE1、GDF15、PTX3、THBS4与SPP1，PTX3、GDF15、THBS4、EXTL1与AREG，NOTCH1、COMP、GDF15、PTX3与POF1B，PTX3、GDF15、THBS4、ADGRE5与GRK5，SPP1、COMP、FCRL1、SOD3与LPL，ADGRE1、GDF15、PTX3、THBS4与LBP，SPP1、COMP、FCRL1、IL4R与LPL，AREG、CEACAM5、PLXDC2、COMP与TNFRSF11A，PTX3、GDF15、RET、ADGRG2与ADGRE2，ADGRE1、KRT19、LMNB2、COMP与PTX3，ADGRE2、SOD3、SPP1、LMNB2与PLXDC1，PTX3、GDF15、THBS4、ADGRG2与PGA4，TMPRSS15、SPP1、COMP、FCRL1与TNC，PTX3、GDF15、THBS4、ADGRE5与IL6，PTX3、POF1B、THBS4、FASLG与ADGRG2，TMPRSS15、PTX3、SPP1、THBS4与SOD3，TMPRSS15、PTX3、SPP1、THBS4与FASLG，PTX3、GDF15、PLXDC2、ADGRE5与POF1B，TMPRSS15、SPP1、FCRL1、SOD3与CEACAM16，TMPRSS15、COMP、FCRL1、TNFRSF10B与AREG，ADGRE1、GDF15、PTX3、THBS4与CKAP4，SPP1、COMP、LMNB2、FASLG与FCRL1，PTX3、SPP1、ENPP6、COMP与DCC，PTX3、GDF15、THBS4、ADGRE5与TNC，GDF15、COMP、LMNB2、DLK1与TCL1A，TMPRSS15、PTX3、GDF15、THBS4与BMP4，SPP1、FCRL1、SOD3、ADGRE5与COMP，TMPRSS15、SPP1、COMP、FCRL1与NOS2，TMPRSS15、PTX3、GDF15、THBS4与PKD1，PTX3、ITGA11、POF1B、THBS4与EXTL1，ADGRE1、GDF15、PTX3、THBS4与CNTN1，PTX3、POF1B、THBS4、ADGRE5与SPP1，TMPRSS15、SPP1、COMP、FCRL1与LBP，PTX3、POF1B、THBS4、EXTL1与PROK1，ITGA11、LMNB2、RET、SOD3与ADGRE1，GNAS、LMNB2、PLXDC2、PROK1与NTRK2，PTX3、GDF15、RET、ADGRG2与HMCN2，PTX3、GDF15、PLXDC2、THBS4与ITM2A，PTX3、GDF15、PLXDC2、ADGRE5与THBS4，CRTAC1、SPP1、TCL1A、SOD3与ADGRG2，GNAS、LMNB2、PLXDC2、PROK1与COMP，PTX3、COMP、HMCN2、POF1B与PGA4，GSN、TMPRSS15、PGA4、PTX3与POF1B，TMPRSS15、PTX3、SPP1、SOD3与PGA4，ADGRE1、GDF15、PTX3、THBS4与GRK5，NOTCH1、COMP、GDF15、PTX3与C9，SPP1、FCRL1、SOD3、ADGRE5与ITIH3，ADGRE2、SOD3、SPP1、LMNB2与COMP，SPP1、PLXDC2、SOD3、IL4R与TCL1A，SPP1、LMNB2、FCRL1、SOD3与BAG3，GNAS、LMNB2、PLXDC2、PROK1与CNTN5，AREG、CEACAM5、PTX3、CD48与LBP，TMPRSS15、SPP1、COMP、TNFRSF10B与PROK1，PTX3、GDF15、THBS4、ADGRE5与RET，GNAS、LMNB2、PLXDC2、PROK1与ESM1，SPP1、LMNB2、FCRL1、SOD3与ADGRG2，SPP1、FCRL1、SOD3、ADGRE5与ADGRG2，PTX3、GDF15、COMP、POF1B与ADGRE1，PTX3、GDF15、COMP、POF1B与HMCN2，TMPRSS15、PTX3、GDF15、THBS4与TNC，PTX3、GDF15、COMP、EXTL1与PGA4，TMPRSS15、PTX3、GDF15、THBS4与PCDH7，ADGRE1、GDF15、PTX3、THBS4与BAG3，GNAS、LMNB2、PLXDC2、PROK1与TMPRSS15，PTX3、ITGA11、POF1B、THBS4与ADGRE1，SPP1、COMP、LMNB2、SOD3与TNC，ADGRE1、GDF15、PTX3、THBS4与ITGB7，PTX3、ITGA11、POF1B、THBS4与PCDH7，TMPRSS15、SPP1、COMP、FCRL1与ENPP6，TMPRSS15、COMP、PTX3、PGA4与CLEC3B，TMPRSS15、SPP1、COMP、FCRL1与LPL，PTX3、GDF15、ADGRG2、ADGRE5与THBS4，COMP、LMNB2、FCRL1、MMP12与SPP1，CRTAC1、SPP1、TCL1A、SOD3与NT5C1A，SPP1、FCRL1、SOD3、ADGRE5与PLXDC1，PTX3、GDF15、COMP、RET与PLXDC2，TMPRSS15、PTX3、GDF15、THBS4与MMP12，GNAS、LMNB2、PLXDC2、PROK1与NT5C1A，PTX3、SPP1、ENPP6、COMP与TMPRSS15，SPP1、FCRL1、SOD3、ADGRE5与CEACAM16，TMPRSS15、PTX3、GDF15、THBS4与PLXDC1，TMPRSS15、SPP1、COMP、FCRL1与PLXDC1，PTX3、GDF15、COMP、ADGRG2与FCRL1，PTX3、SPP1、ENPP6、COMP与ADGRE5，TMPRSS15、SPP1、SOD3、MMP12与CEACAM16，SPP1、LMNB2、FCRL1、SOD3与AGR3，PTX3、GDF15、PLXDC2、THBS4与ADGRE1，PTX3、POF1B、THBS4、EXTL1与ADGRE1，TMPRSS15、PTX3、GDF15、THBS4与ADGRE5，SPP1、COMP、LMNB2、FCRL1与GCG，TMPRSS15、SPP1、COMP、FCRL1与CKAP4，PTX3、GDF15、PLXDC2、THBS4与TNC，PTX3、GDF15、THBS4、FCRL1与ADGRE5，SPP1、ENPP6、FCRL1、ADGRE5与PLXDC1，TMPRSS15、PTX3、GDF15、THBS4与ITM2A，SPP1、COMP、FCRL1、DLK1与LPL，SPP1、FCRL1、SOD3、ADGRE5与CDH23，PTX3、SPP1、COMP、CNTN4与TCL1A，GNAS、LMNB2、PLXDC2、PROK1与IGFBP1，ADGRE1、GDF15、PTX3、THBS4与NPY，ADGRE1、GDF15、PTX3、THBS4与HMCN2，PTX3、GDF15、POF1B、THBS4与NPY，PTX3、GDF15、THBS4、ADGRE5与ITM2A，PTX3、GDF15、THBS4、ADGRE5与TCL1A，PTX3、GDF15、THBS4、ADGRG2与FASLG，NOTCH1、COMP、GDF15、PTX3与ADGRE2，ADGRE1、GDF15、PTX3、THBS4与EDA2R，PTX3、GDF15、COMP、ADGRG2与TCL1A，SPP1、LMNB2、FCRL1、SOD3与GCG，TMPRSS15、SPP1、COMP、FCRL1与PTX3，PTX3、GDF15、ADGRG2、ADGRE5与BMP4，TMPRSS15、SPP1、FCRL1、SOD3与ITIH3，SPP1、COMP、LMNB2、FCRL1与IFNL1，PTX3、SPP1、ENPP6、COMP与TCL1A，TMPRSS15、SPP1、FCRL1、SOD3与LMNB2，PTX3、HMCN2、POF1B、FASLG与ADGRE2，TMPRSS15、SPP1、COMP、FCRL1与NT5C1A，ADGRE1、GDF15、PTX3、THBS4与CD48，GNAS、LMNB2、PLXDC2、PROK1与FGF21，SPP1、PLXDC2、COMP、IL4R与PROK1，TMPRSS15、PTX3、THBS4、FASLG与MMP12，PTX3、POF1B、THBS4、FASLG与IL4R，SPP1、HMCN2、FCRL1、SOD3与PLXDC1，TMPRSS15、COMP、PTX3、PGA4与ENPP6，TMPRSS15、THBS4、CLEC3B、TNFRSF10B与TNC，PTX3、GDF15、PLXDC2、THBS4与PROK1，SPP1、COMP、LMNB2、FCRL1与AREG，ADGRE1、GDF15、PTX3、THBS4与NOS2，SPP1、COMP、LMNB2、FCRL1与ENPP6，SPP1、LMNB2、SOD3、ADGRE5与PROK1，ADGRE1、GDF15、PTX3、THBS4与CEACAM16，ADGRE1、GDF15、PTX3、THBS4与GCG，PTX3、ITGA11、POF1B、THBS4与TCL1A，PTX3、GDF15、ADGRG2、ADGRE5与TCL1A，ADGRE1、GDF15、PTX3、THBS4与RET，SPP1、ENPP6、FCRL1、ADGRE5与ITGA11，AREG、CEACAM5、PTX3、CD48与MMP12，COMP、LMNB2、FCRL1、MMP12与TMPRSS15，PTX3、KRT19、FASLG、ADGRG2与ITM2A，ADGRE1、GDF15、PTX3、THBS4与PGA4，SPP1、COMP、LMNB2、FCRL1与ADGRG2，TMPRSS15、SPP1、FCRL1、SOD3与FGF21，ADGRE1、GDF15、PTX3、THBS4与PTPRS，ADGRE1、GDF15、PTX3、THBS4与C9，TMPRSS15、COMP、PTX3、PGA4与CEACAM5，PTX3、GDF15、COMP、RET与PGA4，PTX3、GDF15、THBS4、ADGRG2与PROK1，ADGRE1、GDF15、PTX3、THBS4与IGSF3，SPP1、FCRL1、SOD3、ADGRE5与PTPRS，ADGRE1、GDF15、PTX3、THBS4与KRT19，SPP1、COMP、FCRL1、SOD3与PROK1，GNAS、LMNB2、PLXDC2、PROK1与AREG，TMPRSS15、SPP1、SOD3、MMP12与PLXDC1，TMPRSS15、SPP1、FCRL1、SOD3与NT5C1A，PTX3、GDF15、COMP、ADGRG2与ADGRE1，TMPRSS15、SPP1、SOD3、MMP12与PGA4，ADGRE1、GDF15、PTX3、THBS4与FAP，SPP1、COMP、LMNB2、FCRL1与ADGRE2，SPP1、COMP、LMNB2、FCRL1与ASAH2，SPP1、FCRL1、SOD3、ADGRE5与C9，TMPRSS15、PTX3、SPP1、THBS4与AREG，PTX3、GDF15、POF1B、THBS4与PCDH7，SPP1、PLXDC2、COMP、LMNB2与BAG3，PTX3、GDF15、RET、ADGRG2与ITM2A，GNAS、LMNB2、PLXDC2、PROK1与SPP1，COMP、FCRL1、GDF15、NOTCH1与PTX3，TMPRSS15、COMP、PTX3、PGA4与IL4R，PTX3、GDF15、POF1B、THBS4与FASLG，PTX3、GDF15、ADGRG2、ADGRE5与ADGRE1，SPP1、COMP、LMNB2、FCRL1与DLK1，SPP1、FCRL1、SOD3、ADGRE5与THBS4，PTX3、POF1B、THBS4、FASLG与CDH23，PTX3、GDF15、PLXDC2、THBS4与BAG3，SPP1、ITGA11、FCRL1、SOD3与TCL1A，ADGRE2、SOD3、SPP1、LMNB2与CRTAC1，ADGRE1、GDF15、PTX3、THBS4与ITGA11，GNAS、LMNB2、PLXDC2、PROK1与BAG3，NOTCH1、COMP、GDF15、PTX3与THBS4，PTX3、LMNB2、SOD3、CNTN4与PGA4，ADGRE1、GDF15、PTX3、THBS4与ASAH2，NOTCH1、COMP、GDF15、PTX3与DCC，CRTAC1、NOTCH1、GDF15、SPP1与TCL1A，TMPRSS15、SPP1、SOD3、MMP12与FCRL1，ADGRE1、GDF15、PTX3、THBS4与ITGAM，PTX3、GDF15、THBS4、EXTL1与ITM2A，ADGRE1、GDF15、PTX3、THBS4与IL6，PTX3、HMCN2、POF1B、FASLG与BMP4，PTX3、GDF15、POF1B、THBS4与EXTL1，PTX3、SPP1、COMP、FCRL1与POF1B，ADGRE1、GDF15、PTX3、THBS4与NT5C1A，NOTCH1、SPP1、TNFRSF10B、COMP与PROK1，NOTCH3、ESM1、PLXDC2、LMNB2与CEACAM5，PTX3、ITGA11、POF1B、THBS4与RET，SPP1、COMP、LMNB2、FCRL1与CDH23，TMPRSS15、PTX3、SPP1、THBS4与FCRL1，PTX3、POF1B、FCRL1、SOD3与PGA4，TMPRSS15、COMP、PTX3、PGA4与MMP12，ADGRE1、GDF15、PTX3、THBS4与RBFOX3，SPP1、COMP、LMNB2、FCRL1与PLXDC1，SPP1、LMNB2、FCRL1、SOD3与PLXDC2，SPP1、COMP、LMNB2、FCRL1与C9，NOTCH1、COMP、GDF15、PTX3与AGR3，SPP1、ENPP6、FCRL1、ADGRE5与COMP，SPP1、COMP、LMNB2、FCRL1与MEGF9，ADGRE1、GDF15、PTX3、THBS4与CNTN4，PTX3、GDF15、RET、ADGRG2与THBS4，PTX3、POF1B、THBS4、EXTL1与ITM2A，PTX3、GDF15、RET、ADGRG2与ADGRE1，SPP1、PLXDC2、FCRL1、SOD3与GCG，TMPRSS15、SPP1、COMP、FCRL1与AREG，SPP1、LMNB2、FCRL1、SOD3与ITGB1，SPP1、COMP、LMNB2、SOD3与PROK1，SPP1、COMP、LMNB2、FCRL1与NOTCH1，PTX3、POF1B、THBS4、FASLG与BMP4，SPP1、PLXDC2、FCRL1、SOD3与ESM1，ADGRE1、GDF15、PTX3、THBS4与CFP，CRTAC1、SPP1、TCL1A、SOD3与ADGRE5，SPP1、COMP、LMNB2、FCRL1与LBP，SPP1、COMP、FCRL1、SOD3与TCL1A，GNAS、LMNB2、PLXDC2、PROK1与THBS4，TMPRSS15、COMP、PTX3、PGA4与SPP1，PTX3、HMCN2、POF1B、FASLG与ITGA11，AREG、CEACAM5、SOD3、RET与FCRL1，ADGRE1、GDF15、PTX3、THBS4与IL4R，PTX3、ITGA11、POF1B、RET与SOD3，ADGRE1、GDF15、PTX3、THBS4与TCL1A，TMPRSS15、PTX3、GDF15、THBS4与RET，TMPRSS15、SPP1、FCRL1、SOD3与PGA4，DCC、CNTN4、PTX3、PGA4与COMP，ADGRE1、GDF15、PTX3、THBS4与CCL7，SPP1、COMP、FCRL1、ADGRE5与LPL，SPP1、COMP、LMNB2、FCRL1与PTPRS，ADGRE1、GDF15、PTX3、THBS4与AREG，TMPRSS15、PTX3、GDF15、THBS4与FGF21，ADGRE1、GDF15、PTX3、THBS4与LMNB2，DCC、CNTN4、PTX3、PGA4与SOD3，TMPRSS15、SPP1、FCRL1、SOD3与LPL，SPP1、PLXDC2、COMP、LMNB2与FCER2，DCC、COMP、SPP1、PROK1与PLXDC2，ADGRE1、GDF15、PTX3、THBS4与CDH23，TMPRSS15、SPP1、ITGA11、SOD3与FCRL1，SPP1、COMP、LMNB2、FCRL1与TCL1A，SPP1、LMNB2、FCRL1、SOD3与ADGRE1，SPP1、THBS4、LMNB2、ADGRE5与CLEC3B，SPP1、COMP、LMNB2、FCRL1与TNC，NOTCH3、ESM1、PLXDC2、LMNB2与AREG，PTX3、POF1B、THBS4、ADGRE5与PGA4，PTX3、GDF15、COMP、THBS4与ADGRE1，TMPRSS15、PTX3、GDF15、THBS4与CCL7，GNAS、LMNB2、PLXDC2、PROK1与ITGA11，SPP1、COMP、LMNB2、FCRL1与TMPRSS15，ADGRE1、GDF15、PTX3、THBS4与TNFRSF10B，PTX3、GDF15、THBS4、ADGRG2与BMP4，CRTAC1、SPP1、TCL1A、SOD3与ADGRE2，SPP1、ITGA11、FCRL1、SOD3与LMNB2，ADGRE1、GDF15、PTX3、THBS4与IFNL1，PTX3、GDF15、POF1B、THBS4与ADGRE5，GNAS、LMNB2、PLXDC2、PROK1与POF1B，DCC、COMP、SPP1、PROK1与ADGRE5，ADGRE1、GDF15、PTX3、THBS4与SPON2，SPP1、LMNB2、FCRL1、SOD3与TCL1A，TMPRSS15、SPP1、FCRL1、SOD3与COMP，ADGRE1、GDF15、PTX3、THBS4与SOD3，PTX3、POF1B、SOD3、EXTL1与PGA4，PTX3、POF1B、THBS4、FASLG与EXTL1，CRTAC1、SPP1、TCL1A、SOD3与TMPRSS15，PTX3、GDF15、PLXDC2、THBS4与POF1B，PTX3、HMCN2、POF1B、FASLG与PLXDC1，PTX3、POF1B、THBS4、FASLG与ITM2A，ADGRE1、GDF15、PTX3、THBS4与CRTAC1，ADGRE1、GDF15、PTX3、THBS4与PKD1，SPP1、COMP、LMNB2、FCRL1与PLXDC2，ADGRE1、GDF15、PTX3、THBS4与ITGA2，SPP1、THBS4、LMNB2、ADGRE5与PROK1，SPP1、COMP、LMNB2、FCRL1与ADGRE1，SPP1、COMP、FCRL1、ADGRE5与LMNB2，PTX3、GDF15、PLXDC2、THBS4与AGR3，TMPRSS15、COMP、PTX3、PGA4与EDA2R，ADGRE1、LMNB2、THBS4、TMPRSS15与GDF15，TMPRSS15、PTX3、GDF15、COMP与ADGRE1，TMPRSS15、SPP1、COMP、FCRL1与PROK1，TMPRSS15、COMP、PTX3、PGA4与CCL7，PTX3、COMP、POF1B、FCRL1与PGA4，ADGRE1、GDF15、PTX3、THBS4与POF1B，ADGRE1、GDF15、PTX3、THBS4与NOTCH3，PTX3、GDF15、THBS4、FASLG与TMPRSS15，GNAS、LMNB2、PLXDC2、PROK1与SOD3，AREG、CEACAM5、RET、LPL与PLXDC2，ADGRE1、GDF15、PTX3、THBS4与PLXDC1，CRTAC1、SPP1、TCL1A、SOD3与LMNB2，TMPRSS15、SPP1、COMP、FCRL1与EDA2R，ADGRE1、GDF15、PTX3、THBS4与LPL，TMPRSS15、PTX3、GDF15、THBS4与PGA4，NOTCH1、COMP、GDF15、PTX3与EXTL1，ADGRE1、GDF15、PTX3、THBS4与GSN，ADGRE2、SOD3、SPP1、LMNB2与FCRL1，PTX3、POF1B、THBS4、FASLG与ITGA11，ADGRE1、GDF15、PTX3、THBS4与BMP4，ADGRE1、GDF15、PTX3、THBS4与DCC，SPP1、COMP、FCRL1、SOD3与CFP，PTX3、POF1B、THBS4、EXTL1与PGA4，SPP1、FCRL1、SOD3、ADGRE5与NT5C1A，COMP、GDF15、NOTCH1、PTX3与TNC，SPP1、COMP、LMNB2、FCRL1与NOS2，ADGRE2、SOD3、SPP1、LMNB2与TCL1A，ADGRE1、GDF15、PTX3、THBS4与PCDH7，ADGRE1、GDF15、PTX3、THBS4与ITM2A，SPP1、LMNB2、FCRL1、SOD3与PLXDC1，GNAS、LMNB2、PLXDC2、PROK1与GDF15，PTX3、GDF15、RET、ADGRG2与COMP，SPP1、COMP、LMNB2、SOD3与ADGRE1，SPP1、FCRL1、SOD3、ADGRE5与TCL1A，TMPRSS15、PTX3、POF1B、THBS4与PGA4，ADGRE1、GDF15、PTX3、THBS4与NOTCH1，SPP1、FCRL1、SOD3、ADGRE5与ITGA11，PTX3、GDF15、THBS4、FASLG与ADGRE1，ADGRE1、GDF15、PTX3、THBS4与ADGRE2，GNAS、LMNB2、PLXDC2、PROK1与MEGF9，AREG、CEACAM5、RET、LPL与VSIG4，SPP1、FCRL1、SOD3、ADGRE5与LMNB2，ADGRE1、GDF15、PTX3、THBS4与IGFBP1，AREG、CEACAM5、PTX3、CD48与ITIH3，SPP1、LMNB2、SOD3、ADGRE5与PLXDC1，ADGRE1、GDF15、PTX3、THBS4与ADGRE5，AREG、CEACAM5、RET、LPL与MEGF9，AREG、CEACAM5、PTX3、CD48与NOTCH1，NOTCH1、COMP、GDF15、PTX3与TCL1A，ADGRE1、GDF15、PTX3、THBS4与TNFRSF11A，SPP1、COMP、LMNB2、FCRL1与LPL，SPP1、COMP、LMNB2、FCRL1与PROK1，TMPRSS15、COMP、PTX3、PGA4与KRT19，AREG、CEACAM5、RET、LPL与SELL，SPP1、COMP、LMNB2、FCRL1与CFP，SPP1、LMNB2、FCRL1、SOD3与MEGF9，ADGRE1、GDF15、PTX3、THBS4与AGR3，SPP1、PLXDC2、COMP、IL4R与TCL1A，ADGRE1、GDF15、PTX3、THBS4与PROK1，TMPRSS15、SPP1、FCRL1、SOD3与PLXDC1，PTX3、GDF15、THBS4、CLEC3B与ADGRE1，NOTCH1、COMP、GDF15、PTX3与PGA4，TMPRSS15、COMP、PTX3、PGA4与GDF15，PTX3、GDF15、ENPP6、THBS4与ADGRE1，PTX3、GDF15、THBS4、EXTL1与ADGRE1，PTX3、GDF15、RET、ADGRG2与BMP4，ADGRE1、GDF15、PTX3、THBS4与TNC，ADGRE2、SOD3、SPP1、LMNB2与PROK1，AREG、CEACAM5、PLXDC2、COMP与VSIG4，SPP1、PLXDC2、COMP、LMNB2与TCL1A，NOTCH1、SPP1、TNFRSF10B、COMP与SERPINA1，TMPRSS15、COMP、PTX3、PGA4与ITM2A，SPP1、PLXDC2、COMP、LMNB2与PROK1，AREG、CEACAM5、RET、LPL与THBS4，AREG、CEACAM5、SOD3、RET与VSIG4，SPP1、COMP、LMNB2、SOD3与TCL1A，AREG、CEACAM5、PTX3、CD48与MEGF9，AREG、CEACAM5、RET、LPL与TCL1A，AREG、CEACAM5、PTX3、CD48与ASAH2，TMPRSS15、PTX3、GDF15、THBS4与ADGRE1，SPP1、COMP、FCRL1、SOD3与LMNB2，SPP1、LMNB2、SOD3、ADGRE5与TCL1A，AREG、CEACAM5、SOD3、RET与ADGRG2，ADGRE1、GDF15、PTX3、THBS4与ADGRG2，SPP1、PLXDC2、SOD3、IL4R与BAG3，SPP1、COMP、LMNB2、FCRL1与CLEC3B，TMPRSS15、COMP、PTX3、PGA4与POF1B，AREG、CEACAM5、SOD3、RET与ADGRE2，AREG、CEACAM5、PLXDC2、COMP与ADGRE2，AREG、CEACAM5、RET、LPL与KRT19，AREG、CEACAM5、PTX3、CD48与KRT19，AREG、CEACAM5、SOD3、RET与CCL7，AREG、CEACAM5、PTX3、CD48与ITM2A，AREG、CEACAM5、PTX3、CD48与CCL7，AREG、CEACAM5、PTX3、SPP1与THBS4，AREG、CEACAM5、PTX3、SPP1与VSIG4，或AREG、CEACAM5、PTX3、SPP1与PLXDC2。Preferably, the 5 markers combination is: TMPRSS15, SPP1, SOD3, MMP12 and ADGRE1, SPP1, COMP, LMNB2, SOD3 and SELL, PTX3, POF1B, THBS4, FASLG and TNC, NOTCH1, COMP, GDF15, PTX3 and FAP, ADGRE1, GDF15, PTX3, THBS4 and IGDCC4, SPP1, COMP, TNFRSF10B, ADGRE5 and PROK1, SPP1, COMP, LMNB2, FCRL1 and PKD1, P TX3, GDF15, RET, ADGRG2 and CD48, TMPRSS15, PTX3, SPP1, THBS4 and PROK1, SPP1, FCRL1, SOD3, ADGRE5 and ITM2A, NOTCH3, ESM1, PLXDC2, LMNB2 and MEGF9, PTX3, HMCN2, POF1B, FASLG and CDH23, PTX3, COMP, POF1B, FASLG and LMNB2, DCC, COMP, SPP1, PROK1 and SOD3, TMPRSS15, SPP1, FCRL1, SOD 3 and NOS2, PTX3, POF1B, THBS4, EXTL1 and SPP1, SPP1, LMNB2, FCRL1, SOD3 and THBS4, COMP, GDF15, NOTCH1, PTX3 and TMPRSS15, TMPRSS15, PTX3, GDF15, THBS4 and LPL, NOTCH1, COMP, GDF15, PTX3 and ADAMTS8, SPP1, LMNB2, SOD3, ADGRE5 and BAG3, SPP1, COMP, FCRL1, SOD3 and PGA4, TMPRSS15, SPP 1. FCRL1, SOD3 and ADGRE5, ADGRE2, SOD3, SPP1, LMNB2 and CLEC3B, PTX3, ITGA11, POF1B, THBS4 and ENPP6, NOTCH1, SPP1, TNFRSF10B, COMP and TCL1A, TMPRSS15, SPP1, FCRL1, SOD3 and PROK1, SPP1, ENPP6, FCRL1, ADGRE5 and THBS4, TMPRSS15, PTX3, GDF15, THBS4 and FCER2, PTX3, GDF15, PLXDC2 , THBS4 and ADGRE2, GNAS, LMNB2, PLXDC2, PROK1 and KRT19, PTX3, GDF15, COMP, ADGRG2 and DCC, TMPRSS15, PTX3, SPP1, THBS4 and IL6, PTX3, GDF15, THBS4, ADGRG2 and FCER2, PTX3, GDF15, PLXDC2, THBS4 and TCL1A, TMPRSS15, PTX3, SPP1, THBS4 and FGF21, GDF15, SPP1, PLXDC2, COMP and PROK1, SP P1, COMP, FCRL1, IL4R and PLXDC2, PTX3, GDF15, RET, ADGRG2 and TCL1A, PTX3, HMCN2, POF1B, FASLG and THBS4, PTX3, GDF15, THBS4, ADGRG2 and BAG3, SPP1, COMP, LMNB2, FCRL1 and ITM2A, ADGRE1, KRT19, LMNB2, COMP and TMPRSS15, DCC, COMP, SPP1, PROK1 and ADAMTS8, PTX3, GDF15, POF1B, THBS4 with CFP, ADGRE1, GDF15, PTX3, THBS4 and DLK1, SPP1, LMNB2, SOD3, ADGRE5 and COMP, TMPRSS15, COMP, PTX3, PGA4 and DCC, GNAS, LMNB2, PLXDC2, PROK1 and IL4R, SPP1, LMNB2, FCRL1, SOD3 and CFP, SPP1, LMNB2, FCRL1, SOD3 and AREG, PTX3, SPP1, COMP, FCRL1 and LMNB2, TMPRSS15, SPP1, FCRL1, SOD 3 and CDH23, TMPRSS15, PTX3, GDF15, THBS4 and AREG, SPP1, COMP, LMNB2, FCRL1 and CNTN4, TMPRSS15, SPP1, COMP, FCRL1 and PTPRS, PTX3, POF1B, THBS4, EXTL1 and BMP4, SPP1, LMNB2, FCRL1, SOD3 and PROK1, TMPRSS15, PTX3, GDF15, THBS4 and IL6, SPP1, ADGRG2, FCRL1, SOD3 and BAG3, PTX3, GDF15, COMP, RET and ADGRE1, SPP1, COMP, FCRL1, SOD3 and PLXDC2, GNAS, LMNB2, PLXDC2, PROK1 and LPL, SPP1, COMP, FCRL1, SOD3 and NOS2, TMPRSS15, COMP, PTX3, PGA4 and SOD3, TMPRSS15, PTX3, GDF15, THBS4 and LBP, PTX3, GDF15, RET, ADGRG2 and ITGA11, SPP1, ENPP6, FCRL1, ADGRE5 and AREG, SPP1, PL XDC2, FCRL1, SOD3 and ITGA11, TMPRSS15, SPP1, FCRL1, SOD3 and THBS4, ADGRE2, SOD3, SPP1, LMNB2 and ITGA11, SPP1, COMP, FCRL1, SOD3 and C9, PTX3, GDF15, THBS4, ADGRE5 and CEACAM16, PTX3, GDF15, RET, ADGRG2 and FASLG, PTX3, POF1B, THBS4, FASLG and TMPRSS15, PTX3, COMP, POF1B, FCRL1 and GDF15, TMPRSS15, PTX3, GDF15, COMP and RET, AREG, CEACAM5, SOD3, RET and CFP, SPP1, PLXDC2, COMP, LMNB2 and GCG, ADGRE1, GDF15, PTX3, THBS4 and CEACAM5, PTX3, GDF15, COMP, ADGRG2 and FASLG, TMPRSS15, COMP, PTX3, PGA4 and FCRL1, PTX3, GDF15, COMP, FASLG and TMPRSS15, TMPRSS15, SPP 1. COMP, FCRL1 and CCL7, PTX3, GDF15, THBS4, CLEC3B and TMPRSS15, PTX3, SPP1, COMP, CNTN4 and TNC, SPP1, COMP, FCRL1, ADGRE5 and PROK1, SPP1, COMP, TNFRSF10B, ADGRE5 and SERPINA1, TMPRSS15, SPP1, COMP, FCRL1 and PGA4, TMPRSS15, COMP, PTX3, PGA4 and IL6, SPP1, FCRL1, SOD3, ADGRE5 and N OS2, TMPRSS15, SPP1, COMP, IL4R and FCRL1, PTX3, COMP, POF1B, FCRL1 and LMNB2, TMPRSS15, PTX3, GDF15, THBS4 and MEGF9, SPP1, COMP, LMNB2, FCRL1 and EDA2R, SPP1, COMP, LMNB2, FCRL1 and GRK5, TMPRSS15, SPP1, COMP, CLEC3B and PGA4, NOTCH1, COMP, GDF15, PTX3 and SPP1, SPP1, COMP, LMNB 2, FCRL1 and ITGB7, ADGRE1, GDF15, PTX3, THBS4 and FGF21, ADGRE1, KRT19, LMNB2, COMP and TCL1A, SPP1, COMP, LMNB2, FCRL1 and ITGB1, TMPRSS15, PTX3, GDF15, THBS4 and PLXDC2, PTX3, POF1B, THBS4, EXTL1 and RET, GNAS, LMNB2, PLXDC2, PROK1 and CNTN4, SPP1, PLXDC2, COMP, IL4R and TNC, PTX3, GDF15, COMP, POF1B and PGA4, SPP1, COMP, LMNB2, FCRL1 and GSN, TMPRSS15, PTX3, SPP1, THBS4 and PGA4, SPP1, COMP, LMNB2, FCRL1 and BAG3, NOTCH1, COMP, GDF15, PTX3 and KRT19, ADGRE1, GDF15, PTX3, THBS4 and SPP1, PTX3, GDF15, THBS4, EXTL1 and AREG, NOTCH1, COMP, GDF15, PTX3 and POF1B, PT X3, GDF15, THBS4, ADGRE5 and GRK5, SPP1, COMP, FCRL1, SOD3 and LPL, ADGRE1, GDF15, PTX3, THBS4 and LBP, SPP1, COMP, FCRL1, IL4R and LPL, AREG, CEACAM5, PLXDC2, COMP and TNFRSF11A, PTX3, GDF15, RET, ADGRG2 and ADGRE2, ADGRE1, KRT19, LMNB2, COMP and PTX3, ADGRE2, SOD3, SPP1, LMNB2 and PL XDC1, PTX3, GDF15, THBS4, ADGRG2 and PGA4, TMPRSS15, SPP1, COMP, FCRL1 and TNC, PTX3, GDF15, THBS4, ADGRE5 and IL6, PTX3, POF1B, THBS4, FASLG and ADGRG2, TMPRSS15, PTX3, SPP1, THBS4 and SOD3, TMPRSS15, PTX3, SPP1, THBS4 and FASLG, PTX3, GDF15, PLXDC2, ADGRE5 and POF1B, TMPRSS15, SPP1, FCRL1, SOD3 and CEACAM16, TMPRSS15, COMP, FCRL1, TNFRSF10B and AREG, ADGRE1, GDF15, PTX3, THBS4 and CKAP4, SPP1, COMP, LMNB2, FASLG and FCRL1, PTX3, SPP1, ENPP6, COMP and DCC, PTX3, GDF15, THBS4, ADGRE5 and TNC, GDF15, COMP, LMNB2, DLK1 and TCL1A, TMPRSS15, PTX3, GDF15, THBS 4 and BMP4, SPP1, FCRL1, SOD3, ADGRE5 and COMP, TMPRSS15, SPP1, COMP, FCRL1 and NOS2, TMPRSS15, PTX3, GDF15, THBS4 and PKD1, PTX3, ITGA11, POF1B, THBS4 and EXTL1, ADGRE1, GDF15, PTX3, THBS4 and CNTN1, PTX3, POF1B, THBS4, ADGRE5 and SPP1, TMPRSS15, SPP1, COMP, FCRL1 and LBP, PTX3, POF 1B, THBS4, EXTL1 and PROK1, ITGA11, LMNB2, RET, SOD3 and ADGRE1, GNAS, LMNB2, PLXDC2, PROK1 and NTRK2, PTX3, GDF15, RET, ADGRG2 and HMCN2, PTX3, GDF15, PLXDC2, THBS4 and ITM2A, PTX3, GDF15, PLXDC2, ADGRE5 and THBS4, CRTAC1, SPP1, TCL1A, SOD3 and ADGRG2, GNAS, LMNB2, PLXDC2, PROK1 and COMP, PTX3, COMP, HMCN2, POF1B and PGA4, GSN, TMPRSS15, PGA4, PTX3 and POF1B, TMPRSS15, PTX3, SPP1, SOD3 and PGA4, ADGRE1, GDF15, PTX3, THBS4 and GRK5, NOTCH1, COMP, GDF15, PTX3 and C9, SPP1, FCRL1, SOD3, ADGRE5 and ITIH3, ADGRE2, SOD3, SPP1, LMNB2 and COMP, SPP1, PLXDC2, SOD3, IL4 R and TCL1A, SPP1, LMNB2, FCRL1, SOD3 and BAG3, GNAS, LMNB2, PLXDC2, PROK1 and CNTN5, AREG, CEACAM5, PTX3, CD48 and LBP, TMPRSS15, SPP1, COMP, TNFRSF10B and PROK1, PTX3, GDF15, THBS4, ADGRE5 and RET, GNAS, LMNB2, PLXDC2, PROK1 and ESM1, SPP1, LMNB2, FCRL1, SOD3 and ADGRG2, SPP1, FCRL1 , SOD3, ADGRE5 and ADGRG2, PTX3, GDF15, COMP, POF1B and ADGRE1, PTX3, GDF15, COMP, POF1B and HMCN2, TMPRSS15, PTX3, GDF15, THBS4 and TNC, PTX3, GDF15, COMP, EXTL1 and PGA4, TMPRSS15, PTX3, GDF15, THBS4 and PCDH7, ADGRE1, GDF15, PTX3, THBS4 and BAG3, GNAS, LMNB2, PLXDC2, PROK1 and TMP RSS15, PTX3, ITGA11, POF1B, THBS4 and ADGRE1, SPP1, COMP, LMNB2, SOD3 and TNC, ADGRE1, GDF15, PTX3, THBS4 and ITGB7, PTX3, ITGA11, POF1B, THBS4 and PCDH7, TMPRSS15, SPP1, COMP, FCRL1 and ENPP6, TMPRSS15, COMP, PTX3, PGA4 and CLEC3B, TMPRSS15, SPP1, COMP, FCRL1 and LPL, PTX3, GDF15 , ADGRG2, ADGRE5 and THBS4, COMP, LMNB2, FCRL1, MMP12 and SPP1, CRTAC1, SPP1, TCL1A, SOD3 and NT5C1A, SPP1, FCRL1, SOD3, ADGRE5 and PLXDC1, PTX3, GDF15, COMP, RET and PLXDC2, TMPRSS15, PTX3, GDF15, THBS4 and MMP12, GNAS, LMNB2, PLXDC2, PROK1 and NT5C1A, PTX3, SPP1, ENPP6, COMP and TM PRSS15, SPP1, FCRL1, SOD3, ADGRE5 and CEACAM16, TMPRSS15, PTX3, GDF15, THBS4 and PLXDC1, TMPRSS15, SPP1, COMP, FCRL1 and PLXDC1, PTX3, GDF15, COMP, ADGRG2 and FCRL1, PTX3, SPP1, ENPP6, COMP and ADGRE5, TMPRSS15, SPP1, SOD3, MMP12 and CEACAM16, SPP1, LMNB2, FCRL1, SOD3 and AGR3, P TX3, GDF15, PLXDC2, THBS4 and ADGRE1, PTX3, POF1B, THBS4, EXTL1 and ADGRE1, TMPRSS15, PTX3, GDF15, THBS4 and ADGRE5, SPP1, COMP, LMNB2, FCRL1 and GCG, TMPRSS15, SPP1, COMP, FCRL1 and CKAP4, PTX3, GDF15, PLXDC2, THBS4 and TNC, PTX3, GDF15, THBS4, FCRL1 and ADGRE5, SPP1, ENPP6, FCR L1, ADGRE5 and PLXDC1, TMPRSS15, PTX3, GDF15, THBS4 and ITM2A, SPP1, COMP, FCRL1, DLK1 and LPL, SPP1, FCRL1, SOD3, ADGRE5 and CDH23, PTX3, SPP1, COMP, CNTN4 and TCL1A, GNAS, LMNB2, PLXDC2, PROK1 and IGFBP1, ADGRE1, GDF15, PTX3, THBS4 and NPY, ADGRE1, GDF15, PTX3, THBS4 and HMCN2, PTX3 , GDF15, POF1B, THBS4 and NPY, PTX3, GDF15, THBS4, ADGRE5 and ITM2A, PTX3, GDF15, THBS4, ADGRE5 and TCL1A, PTX3, GDF15, THBS4, ADGRG2 and FASLG, NOTCH1, COMP, GDF15, PTX3 and ADGRE2, ADGRE1, GDF15, PTX3, THBS4 and EDA2R, PTX3, GDF15, COMP, ADGRG2 and TCL1A, SPP1, LMNB2, FCRL1, SOD 3 and GCG, TMPRSS15, SPP1, COMP, FCRL1 and PTX3, PTX3, GDF15, ADGRG2, ADGRE5 and BMP4, TMPRSS15, SPP1, FCRL1, SOD3 and ITIH3, SPP1, COMP, LMNB2, FCRL1 and IFNL1, PTX3, SPP1, ENPP6, COMP and TCL1A, TMPRSS15, SPP1, FCRL1, SOD3 and LMNB2, PTX3, HMCN2, POF1B, FASLG and ADGRE2, TMPRSS15, S PP1, COMP, FCRL1 and NT5C1A, ADGRE1, GDF15, PTX3, THBS4 and CD48, GNAS, LMNB2, PLXDC2, PROK1 and FGF21, SPP1, PLXDC2, COMP, IL4R and PROK1, TMPRSS15, PTX3, THBS4, FASLG and MMP12, PTX3, POF1B, THBS4, FASLG and IL4R, SPP1, HMCN2, FCRL1, SOD3 and PLXDC1, TMPRSS15, COMP, PTX3, PGA4 and ENPP6, TMPRSS15, THBS4, CLEC3B, TNFRSF10B and TNC, PTX3, GDF15, PLXDC2, THBS4 and PROK1, SPP1, COMP, LMNB2, FCRL1 and AREG, ADGRE1, GDF15, PTX3, THBS4 and NOS2, SPP1, COMP, LMNB2, FCRL1 and ENPP6, SPP1, LMNB2, SOD3, ADGRE5 and PROK1, ADGRE1, GDF15, PTX3, THBS4 and CEACAM16, ADGRE 1. GDF15, PTX3, THBS4 and GCG, PTX3, ITGA11, POF1B, THBS4 and TCL1A, PTX3, GDF15, ADGRG2, ADGRE5 and TCL1A, ADGRE1, GDF15, PTX3, THBS4 and RET, SPP1, ENPP6, FCRL1, ADGRE5 and ITGA11, AREG, CEACAM5, PTX3, CD48 and MMP12, COMP, LMNB2, FCRL1, MMP12 and TMPRSS15, PTX3, KRT19, FASLG, A DGRG2 and ITM2A, ADGRE1, GDF15, PTX3, THBS4 and PGA4, SPP1, COMP, LMNB2, FCRL1 and ADGRG2, TMPRSS15, SPP1, FCRL1, SOD3 and FGF21, ADGRE1, GDF15, PTX3, THBS4 and PTPRS, ADGRE1, GDF15, PTX3, THBS4 and C9, TMPRSS15, COMP, PTX3, PGA4 and CEACAM5, PTX3, GDF15, COMP, RET and PGA4, PTX3, GDF 15, THBS4, ADGRG2 and PROK1, ADGRE1, GDF15, PTX3, THBS4 and IGSF3, SPP1, FCRL1, SOD3, ADGRE5 and PTPRS, ADGRE1, GDF15, PTX3, THBS4 and KRT19, SPP1, COMP, FCRL1, SOD3 and PROK1, GNAS, LMNB2, PLXDC2, PROK1 and AREG, TMPRSS15, SPP1, SOD3, MMP12 and PLXDC1, TMPRSS15, SPP1, FCRL1, SOD 3 and NT5C1A, PTX3, GDF15, COMP, ADGRG2 and ADGRE1, TMPRSS15, SPP1, SOD3, MMP12 and PGA4, ADGRE1, GDF15, PTX3, THBS4 and FAP, SPP1, COMP, LMNB2, FCRL1 and ADGRE2, SPP1, COMP, LMNB2, FCRL1 and ASAH2, SPP1, FCRL1, SOD3, ADGRE5 and C9, TMPRSS15, PTX3, SPP1, THBS4 and AREG, PTX3, GDF15, PO F1B, THBS4 and PCDH7, SPP1, PLXDC2, COMP, LMNB2 and BAG3, PTX3, GDF15, RET, ADGRG2 and ITM2A, GNAS, LMNB2, PLXDC2, PROK1 and SPP1, COMP, FCRL1, GDF15, NOTCH1 and PTX3, TMPRSS15, COMP, PTX3, PGA4 and IL4R, PTX3, GDF15, POF1B, THBS4 and FASLG, PTX3, GDF15, ADGRG2, ADGRE1 and SP P1, COMP, LMNB2, FCRL1 and DLK1, SPP1, FCRL1, SOD3, ADGRE5 and THBS4, PTX3, POF1B, THBS4, FASLG and CDH23, PTX3, GDF15, PLXDC2, THBS4 and BAG3, SPP1, ITGA11, FCRL1, SOD3 and TCL1A, ADGRE2, SOD3, SPP1, LMNB2 and CRTAC1, ADGRE1, GDF15, PTX3, THBS4 and ITGA11, GNAS, LMNB2, PLXDC2, PRO K1 and BAG3, NOTCH1, COMP, GDF15, PTX3 and THBS4, PTX3, LMNB2, SOD3, CNTN4 and PGA4, ADGRE1, GDF15, PTX3, THBS4 and ASAH2, NOTCH1, COMP, GDF15, PTX3 and DCC, CRTAC1, NOTCH1, GDF15, SPP1 and TCL1A, TMPRSS15, SPP1, SOD3, MMP12 and FCRL1, ADGRE1, GDF15, PTX3, THBS4 and ITGAM, PTX3, GDF1 5. THBS4, EXTL1 and ITM2A, ADGRE1, GDF15, PTX3, THBS4 and IL6, PTX3, HMCN2, POF1B, FASLG and BMP4, PTX3, GDF15, POF1B, THBS4 and EXTL1, PTX3, SPP1, COMP, FCRL1 and POF1B, ADGRE1, GDF15, PTX3, THBS4 and NT5C1A, NOTCH1, SPP1, TNFRSF10B, COMP and PROK1, NOTCH3, ESM1, PLXDC2, LMNB2 and CE ACAM5, PTX3, ITGA11, POF1B, THBS4 and RET, SPP1, COMP, LMNB2, FCRL1 and CDH23, TMPRSS15, PTX3, SPP1, THBS4 and FCRL1, PTX3, POF1B, FCRL1, SOD3 and PGA4, TMPRSS15, COMP, PTX3, PGA4 and MMP12, ADGRE1, GDF15, PTX3, THBS4 and RBFOX3, SPP1, COMP, LMNB2, FCRL1 and PLXDC1, SPP1, LMNB2, F CRL1, SOD3 and PLXDC2, SPP1, COMP, LMNB2, FCRL1 and C9, NOTCH1, COMP, GDF15, PTX3 and AGR3, SPP1, ENPP6, FCRL1, ADGRE5 and COMP, SPP1, COMP, LMNB2, FCRL1 and MEGF9, ADGRE1, GDF15, PTX3, THBS4 and CNTN4, PTX3, GDF15, RET, ADGRG2 and THBS4, PTX3, POF1B, THBS4, EXTL1 and ITM2A, PTX3, GDF1 5. RET, ADGRG2 and ADGRE1, SPP1, PLXDC2, FCRL1, SOD3 and GCG, TMPRSS15, SPP1, COMP, FCRL1 and AREG, SPP1, LMNB2, FCRL1, SOD3 and ITGB1, SPP1, COMP, LMNB2, SOD3 and PROK1, SPP1, COMP, LMNB2, FCRL1 and NOTCH1, PTX3, POF1B, THBS4, FASLG and BMP4, SPP1, PLXDC2, FCRL1, SOD3 and ESM1, ADGRE 1, GDF15, PTX3, THBS4 and CFP, CRTAC1, SPP1, TCL1A, SOD3 and ADGRE5, SPP1, COMP, LMNB2, FCRL1 and LBP, SPP1, COMP, FCRL1, SOD3 and TCL1A, GNAS, LMNB2, PLXDC2, PROK1 and THBS4, TMPRSS15, COMP, PTX3, PGA4 and SPP1, PTX3, HMCN2, POF1B, FASLG and ITGA11, AREG, CEACAM5, SOD3, RET and FCRL1, ADGRE1, GDF15, PTX3, THBS4 and IL4R, PTX3, ITGA11, POF1B, RET and SOD3, ADGRE1, GDF15, PTX3, THBS4 and TCL1A, TMPRSS15, PTX3, GDF15, THBS4 and RET, TMPRSS15, SPP1, FCRL1, SOD3 and PGA4, DCC, CNTN4, PTX3, PGA4 and COMP, ADGRE1, GDF15, PTX3, THBS4 and CCL7, SPP1, COMP, FCRL1, ADGRE5 with LPL, SPP1, COMP, LMNB2, FCRL1 and PTPRS, ADGRE1, GDF15, PTX3, THBS4 and AREG, TMPRSS15, PTX3, GDF15, THBS4 and FGF21, ADGRE1, GDF15, PTX3, THBS4 and LMNB2, DCC, CNTN4, PTX3, PGA4 and SOD3, TMPRSS15, SPP1, FCRL1, SOD3 and LPL, SPP1, PLXDC2, COMP, LMNB2 and FCER2, DCC, COMP, SPP1, PR OK1 and PLXDC2, ADGRE1, GDF15, PTX3, THBS4 and CDH23, TMPRSS15, SPP1, ITGA11, SOD3 and FCRL1, SPP1, COMP, LMNB2, FCRL1 and TCL1A, SPP1, LMNB2, FCRL1, SOD3 and ADGRE1, SPP1, THBS4, LMNB2, ADGRE5 and CLEC3B, SPP1, COMP, LMNB2, FCRL1 and TNC, NOTCH3, ESM1, PLXDC2, LMNB2 and AREG, PTX3, POF1B, THBS4, ADGRE5 and PGA4, PTX3, GDF15, COMP, THBS4 and ADGRE1, TMPRSS15, PTX3, GDF15, THBS4 and CCL7, GNAS, LMNB2, PLXDC2, PROK1 and ITGA11, SPP1, COMP, LMNB2, FCRL1 and TMPRSS15, ADGRE1, GDF15, PTX3, THBS4 and TNFRSF10B, PTX3, GDF15, THBS4, ADGRG2 and BMP4, CRTAC1, SPP1, TC L1A, SOD3 and ADGRE2, SPP1, ITGA11, FCRL1, SOD3 and LMNB2, ADGRE1, GDF15, PTX3, THBS4 and IFNL1, PTX3, GDF15, POF1B, THBS4 and ADGRE5, GNAS, LMNB2, PLXDC2, PROK1 and POF1B, DCC, COMP, SPP1, PROK1 and ADGRE5, ADGRE1, GDF15, PTX3, THBS4 and SPON2, SPP1, LMNB2, FCRL1, SOD3 and TCL1A, TM PRSS15, SPP1, FCRL1, SOD3 and COMP, ADGRE1, GDF15, PTX3, THBS4 and SOD3, PTX3, POF1B, SOD3, EXTL1 and PGA4, PTX3, POF1B, THBS4, FASLG and EXTL1, CRTAC1, SPP1, TCL1A, SOD3 and TMPRSS15, PTX3, GDF15, PLXDC2, THBS4 and POF1B, PTX3, HMCN2, POF1B, FASLG and PLXDC1, PTX3, POF1B, THBS4, F ASLG and ITM2A, ADGRE1, GDF15, PTX3, THBS4 and CRTAC1, ADGRE1, GDF15, PTX3, THBS4 and PKD1, SPP1, COMP, LMNB2, FCRL1 and PLXDC2, ADGRE1, GDF15, PTX3, THBS4 and ITGA2, SPP1, THBS4, LMNB2, ADGRE5 and PROK1, SPP1, COMP, LMNB2, FCRL1 and ADGRE1, SPP1, COMP, FCRL1, ADGRE5 and LMNB2, PTX3 , GDF15, PLXDC2, THBS4 and AGR3, TMPRSS15, COMP, PTX3, PGA4 and EDA2R, ADGRE1, LMNB2, THBS4, TMPRSS15 and GDF15, TMPRSS15, PTX3, GDF15, COMP and ADGRE1, TMPRSS15, SPP1, COMP, FCRL1 and PROK1, TMPRSS15, COMP, PTX3, PGA4 and CCL7, PTX3, COMP, POF1B, FCRL1 and PGA4, ADGRE1, GDF15, PT X3, THBS4 and POF1B, ADGRE1, GDF15, PTX3, THBS4 and NOTCH3, PTX3, GDF15, THBS4, FASLG and TMPRSS15, GNAS, LMNB2, PLXDC2, PROK1 and SOD3, AREG, CEACAM5, RET, LPL and PLXDC2, ADGRE1, GDF15, PTX3, THBS4 and PLXDC1, CRTAC1, SPP1, TCL1A, SOD3 and LMNB2, TMPRSS15, SPP1, COMP, FCRL1 and ED A2R, ADGRE1, GDF15, PTX3, THBS4 and LPL, TMPRSS15, PTX3, GDF15, THBS4 and PGA4, NOTCH1, COMP, GDF15, PTX3 and EXTL1, ADGRE1, GDF15, PTX3, THBS4 and GSN, ADGRE2, SOD3, SPP1, LMNB2 and FCRL1, PTX3, POF1B, THBS4, FASLG and ITGA11, ADGRE1, GDF15, PTX3, THBS4 and BMP4, ADGRE1, GDF15, PT X3, THBS4 and DCC, SPP1, COMP, FCRL1, SOD3 and CFP, PTX3, POF1B, THBS4, EXTL1 and PGA4, SPP1, FCRL1, SOD3, ADGRE5 and NT5C1A, COMP, GDF15, NOTCH1, PTX3 and TNC, SPP1, COMP, LMNB2, FCRL1 and NOS2, ADGRE2, SOD3, SPP1, LMNB2 and TCL1A, ADGRE1, GDF15, PTX3, THBS4 and PCDH7, ADGRE1, GDF15, PTX3, THBS4 and ITM2A, SPP1, LMNB2, FCRL1, SOD3 and PLXDC1, GNAS, LMNB2, PLXDC2, PROK1 and GDF15, PTX3, GDF15, RET, ADGRG2 and COMP, SPP1, COMP, LMNB2, SOD3 and ADGRE1, SPP1, FCRL1, SOD3, ADGRE5 and TCL1A, TMPRSS15, PTX3, POF1B, THBS4 and PGA4, ADGRE1, GDF15, PTX3, THBS4 and NOTCH1, S PP1, FCRL1, SOD3, ADGRE5 and ITGA11, PTX3, GDF15, THBS4, FASLG and ADGRE1, ADGRE1, GDF15, PTX3, THBS4 and ADGRE2, GNAS, LMNB2, PLXDC2, PROK1 and MEGF9, AREG, CEACAM5, RET, LPL and VSIG4, SPP1, FCRL1, SOD3, ADGRE5 and LMNB2, ADGRE1, GDF15, PTX3, THBS4 and IGFBP1, AREG, CEACAM5, PT X3, CD48 and ITIH3, SPP1, LMNB2, SOD3, ADGRE5 and PLXDC1, ADGRE1, GDF15, PTX3, THBS4 and ADGRE5, AREG, CEACAM5, RET, LPL and MEGF9, AREG, CEACAM5, PTX3, CD48 and NOTCH1, NOTCH1, COMP, GDF15, PTX3 and TCL1A, ADGRE1, GDF15, PTX3, THBS4 and TNFRSF11A, SPP1, COMP, LMNB2, FCRL1 and LPL, SP P1, COMP, LMNB2, FCRL1 and PROK1, TMPRSS15, COMP, PTX3, PGA4 and KRT19, AREG, CEACAM5, RET, LPL and SELL, SPP1, COMP, LMNB2, FCRL1 and CFP, SPP1, LMNB2, FCRL1, SOD3 and MEGF9, ADGRE1, GDF15, PTX3, THBS4 and AGR3, SPP1, PLXDC2, COMP, IL4R and TCL1A, ADGRE1, GDF15, PTX3, THBS4 and PROK1 , TMPRSS15, SPP1, FCRL1, SOD3 and PLXDC1, PTX3, GDF15, THBS4, CLEC3B and ADGRE1, NOTCH1, COMP, GDF15, PTX3 and PGA4, TMPRSS15, COMP, PTX3, PGA4 and GDF15, PTX3, GDF15, ENPP6, THBS4 and ADGRE1, PTX3, GDF15, THBS4, EXTL1 and ADGRE1, PTX3, GDF15, RET, ADGRG2 and BMP4, ADGRE1, GDF15, P TX3, THBS4 and TNC, ADGRE2, SOD3, SPP1, LMNB2 and PROK1, AREG, CEACAM5, PLXDC2, COMP and VSIG4, SPP1, PLXDC2, COMP, LMNB2 and TCL1A, NOTCH1, SPP1, TNFRSF10B, COMP and SERPINA1, TMPRSS15, COMP, PTX3, PGA4 and ITM2A, SPP1, PLXDC2, COMP, LMNB2 and PROK1, AREG, CEACAM5, RET, LPL and THB S4, AREG, CEACAM5, SOD3, RET and VSIG4, SPP1, COMP, LMNB2, SOD3 and TCL1A, AREG, CEACAM5, PTX3, CD48 and MEGF9, AREG, CEACAM5, RET, LPL and TCL1A, AREG, CEACAM5, PTX3, CD48 and ASAH2, TMPRSS15, PTX3, GDF15, THBS4 and ADGRE1, SPP1, COMP, FCRL1, SOD3 and LMNB2, SPP1, LMNB2, SOD3, ADGR E5 and TCL1A, AREG, CEACAM5, SOD3, RET and ADGRG2, ADGRE1, GDF15, PTX3, THBS4 and ADGRG2, SPP1, PLXDC2, SOD3, IL4R and BAG3, SPP1, COMP, LMNB2, FCRL1 and CLEC3B, TMPRSS15, COMP, PTX3, PGA4 and POF1B, AREG, CEACAM5, SOD3, RET and ADGRG2, AREG, CEACAM5, PLXDC2, COMP and ADGRE2, EACAM5, RET, LPL, and KRT19, AREG, CEACAM5, PTX3, CD48, and KRT19, AREG, CEACAM5, SOD3, RET, and CCL7, AREG, CEACAM5, PTX3, CD48, and ITM2A, AREG, CEACAM5, PTX3, CD48, and CCL7, AREG, CEACAM5, PTX3, SPP1, and THBS4, AREG, CEACAM5, PTX3, SPP1, and VSIG4, or AREG, CEACAM5, PTX3, SPP1, and PLXDC2.
优选地，所述5markers组合为：COMP、FCRL1、GDF15、NOTCH1与PTX3，PTX3、COMP、POF1B、FASLG与LMNB2，GDF15、SPP1、PLXDC2、COMP与PROK1，SPP1、ADGRG2、FCRL1、SOD3与BAG3，PTX3、GDF15、COMP、FASLG与TMPRSS15，PTX3、GDF15、THBS4、CLEC3B与TMPRSS15，SPP1、COMP、TNFRSF10B、ADGRE5与SERPINA1，SPP1、COMP、FCRL1、IL4R与LPL，ADGRE1、KRT19、LMNB2、COMP与PTX3，SPP1、COMP、LMNB2、FASLG与FCRL1，PTX3、POF1B、THBS4、ADGRE5与SPP1，ITGA11、LMNB2、RET、SOD3与ADGRE1，PTX3、COMP、HMCN2、POF1B与PGA4，GSN、TMPRSS15、PGA4、PTX3与POF1B，PTX3、GDF15、COMP、EXTL1与PGA4，PTX3、GDF15、COMP、RET与PLXDC2，SPP1、COMP、FCRL1、DLK1与LPL，PTX3、GDF15、THBS4、ADGRE5与TCL1A，PTX3、SPP1、ENPP6、COMP与TCL1A，TMPRSS15、PTX3、THBS4、FASLG与MMP12，SPP1、HMCN2、FCRL1、SOD3与PLXDC1，TMPRSS15、THBS4、CLEC3B、TNFRSF10B与TNC，PTX3、ITGA11、POF1B、THBS4与TCL1A，COMP、LMNB2、FCRL1、MMP12与TMPRSS15，PTX3、KRT19、FASLG、ADGRG2与ITM2A，PTX3、GDF15、THBS4、ADGRG2与PROK1，PTX3、GDF15、COMP、ADGRG2与ADGRE1，TMPRSS15、SPP1、SOD3、MMP12与PGA4，PTX3、LMNB2、SOD3、CNTN4与PGA4，CRTAC1、NOTCH1、GDF15、SPP1与TCL1A，PTX3、GDF15、THBS4、EXTL1与ITM2A，PTX3、SPP1、COMP、FCRL1与POF1B，PTX3、POF1B、FCRL1、SOD3与PGA4，PTX3、ITGA11、POF1B、RET与SOD3，PTX3、GDF15、COMP、THBS4与ADGRE1，SPP1、ITGA11、FCRL1、SOD3与LMNB2，DCC、COMP、SPP1、PROK1与ADGRE5，SPP1、THBS4、LMNB2、ADGRE5与PROK1，SPP1、COMP、FCRL1、ADGRE5与LMNB2，PTX3、GDF15、PLXDC2、THBS4与AGR3，ADGRE1、LMNB2、THBS4、TMPRSS15与GDF15，PTX3、COMP、POF1B、FCRL1与PGA4，CRTAC1、SPP1、TCL1A、SOD3与LMNB2，PTX3、POF1B、THBS4、EXTL1与PGA4，TMPRSS15、PTX3、POF1B、THBS4与PGA4，SPP1、LMNB2、FCRL1、SOD3与MEGF9，TMPRSS15、SPP1、FCRL1、SOD3与PLXDC1，NOTCH1、COMP、GDF15、PTX3与PGA4，PTX3、GDF15、ENPP6、THBS4与ADGRE1，PTX3、GDF15、RET、ADGRG2与BMP4，SPP1、PLXDC2、COMP、LMNB2与PROK1，SPP1、COMP、LMNB2、SOD3与TCL1A，TMPRSS15、PTX3、GDF15、THBS4与ADGRE1，SPP1、LMNB2、SOD3、ADGRE5与TCL1A，ADGRE1、GDF15、PTX3、THBS4与ADGRG2，SPP1、PLXDC2、SOD3、IL4R与BAG3，SPP1、COMP、LMNB2、FCRL1与CLEC3B，TMPRSS15、COMP、PTX3、PGA4与POF1B，AREG、CEACAM5、PLXDC2、COMP与ADGRE2，AREG、CEACAM5、RET、LPL与KRT19，AREG、CEACAM5、SOD3、RET与CCL7，AREG、CEACAM5、PTX3、CD48与CCL7，或AREG、CEACAM5、PTX3、SPP1与PLXDC2；即上述63个5markers组合中的任意一种。Preferably, the 5 markers combination is: COMP, FCRL1, GDF15, NOTCH1 and PTX3, PTX3, COMP, POF1B, FASLG and LMNB2, GDF15, SPP1, PLXDC2, COMP and PROK1, SPP1, ADGRG2, FCRL1, SOD3 and BAG3, PTX3, GDF15, COMP, FASLG and TMPRSS15, PTX3, GDF15, THBS4, CLEC3B and TMPRSS15, SPP1, COMP, TNFRSF10B, ADGRE5 and SERPINA1, SPP 1. COMP, FCRL1, IL4R and LPL, ADGRE1, KRT19, LMNB2, COMP and PTX3, SPP1, COMP, LMNB2, FASLG and FCRL1, PTX3, POF1B, THBS4, ADGRE5 and SPP1, ITGA11, LMNB2, RET, SOD3 and ADGRE1, PTX3, COMP, HMCN2, POF1B and PGA4, GSN, TMPRSS15, PGA4, PTX3 and POF1B, PTX3, GDF15, COMP, EXTL1 and PGA4, PTX3, GDF15, COMP , RET and PLXDC2, SPP1, COMP, FCRL1, DLK1 and LPL, PTX3, GDF15, THBS4, ADGRE5 and TCL1A, PTX3, SPP1, ENPP6, COMP and TCL1A, TMPRSS15, PTX3, THBS4, FASLG and MMP12, SPP1, HMCN2, FCRL1, SOD3 and PLXDC1, TMPRSS15, THBS4, CLEC3B, TNFRSF10B and TNC, PTX3, ITGA11, POF1B, THBS4 and TCL1A, COMP, LMNB2, FCR L1, MMP12 and TMPRSS15, PTX3, KRT19, FASLG, ADGRG2 and ITM2A, PTX3, GDF15, THBS4, ADGRG2 and PROK1, PTX3, GDF15, COMP, ADGRG2 and ADGRE1, TMPRSS15, SPP1, SOD3, MMP12 and PGA4, PTX3, LMNB2, SOD3, CNTN4 and PGA4, CRTAC1, NOTCH1, GDF15, SPP1 and TCL1A, PTX3, GDF15, THBS4, EXTL1 and ITM2A, PTX3, SPP1, COMP, FCRL1 and POF1B, PTX3, POF1B, FCRL1, SOD3 and PGA4, PTX3, ITGA11, POF1B, RET and SOD3, PTX3, GDF15, COMP, THBS4 and ADGRE1, SPP1, ITGA11, FCRL1, SOD3 and LMNB2, DCC, COMP, SPP1, PROK1 and ADGRE5, SPP1, THBS4, LMNB2, ADGRE5 and PROK1, SPP1, COMP, FCRL1, ADGRE5 and LMNB2, PTX3, GDF15, PLXDC2, TH BS4 and AGR3, ADGRE1, LMNB2, THBS4, TMPRSS15 and GDF15, PTX3, COMP, POF1B, FCRL1 and PGA4, CRTAC1, SPP1, TCL1A, SOD3 and LMNB2, PTX3, POF1B, THBS4, EXTL1 and PGA4, TMPRSS15, PTX3, POF1B, THBS4 and PGA4, SPP1, LMNB2, FCRL1, SOD3 and MEGF9, TMPRSS15, SPP1, FCRL1, SOD3 and PLXDC1, NOTCH1, COMP, GDF15 , PTX3 and PGA4, PTX3, GDF15, ENPP6, THBS4 and ADGRE1, PTX3, GDF15, RET, ADGRG2 and BMP4, SPP1, PLXDC2, COMP, LMNB2 and PROK1, SPP1, COMP, LMNB2, SOD3 and TCL1A, TMPRSS15, PTX3, GDF15, THBS4 and ADGRE1, SPP1, LMNB2, SOD3, ADGRE5 and TCL1A, ADGRE1, GDF15, PTX3, THBS4 and ADGRG2, SPP1, PLXDC2, SOD3, I L4R and BAG3, SPP1, COMP, LMNB2, FCRL1 and CLEC3B, TMPRSS15, COMP, PTX3, PGA4 and POF1B, AREG, CEACAM5, PLXDC2, COMP and ADGRE2, AREG, CEACAM5, RET, LPL and KRT19, AREG, CEACAM5, SOD3, RET and CCL7, AREG, CEACAM5, PTX3, CD48 and CCL7, or AREG, CEACAM5, PTX3, SPP1 and PLXDC2; that is, any one of the above 63 5-marker combinations.
优选地，所述5markers组合为所述E中的任意五种。Preferably, the 5 markers are combined into any five of the E.
优选地，所述5markers组合为：COMP、GDF15、NOTCH1、PTX3与TMPRSS15，COMP、FCRL1、GDF15、NOTCH1与PTX3，COMP、GDF15、NOTCH1、PTX3与TNC，COMP、EDA2R、GDF15、NOTCH1与PTX3，CEACAM5、COMP、GDF15、NOTCH1与PTX3，COMP、FCRL1、GDF15、PTX3与TMPRSS15，COMP、EDA2R、GDF15、PTX3与TMPRSS15，COMP、GDF15、PTX3、TMPRSS15与TNC，COMP、GDF15、NOTCH1、TMPRSS15与TNC，COMP、EDA2R、FCRL1、PTX3与TMPRSS15，CEACAM5、COMP、GDF15、PTX3与TNC，AREG、CEACAM5、COMP、GDF15与NOTCH1，COMP、EDA2R、FCRL1、TMPRSS15与TNC，COMP、EDA2R、PTX3、TMPRSS15与TNC，CEACAM5、GDF15、NOTCH1、PTX3与TNC，COMP、GDF15、NOTCH1、PTX3与SERPINA1，AREG、COMP、FCRL1、GDF15与TMPRSS15，CEACAM5、COMP、GDF15、NOTCH1与TNC，AREG、COMP、EDA2R、PTX3与TMPRSS15，CEACAM5、COMP、GDF15、PTX3与TMPRSS15，GDF15、NOTCH1、PTX3、TMPRSS15与TNC，AREG、COMP、GDF15、NOTCH1与PTX3，CEACAM5、GDF15、NOTCH1、TMPRSS15与TNC，CEACAM5、COMP、GDF15、TMPRSS15与TNC，AREG、COMP、EDA2R、FCRL1与TMPRSS15，COMP、FCRL1、GDF15、PTX3与TNC，AREG、CEACAM5、COMP、EDA2R与TMPRSS15，COMP、FCRL1、GDF15、NOTCH1与TMPRSS15，AREG、CEACAM5、COMP、GDF15与PTX3，AREG、CEACAM5、COMP、GDF15与TMPRSS15，COMP、EDA2R、FCRL1、GDF15与PTX3，COMP、FCRL1、GDF15、NOTCH1与SERPINA1，COMP、EDA2R、FCRL1、SERPINA1与TMPRSS15，COMP、EDA2R、GDF15、TMPRSS15与TNC，COMP、FCRL1、GDF15、NOTCH1与TNC，COMP、GDF15、PTX3、SERPINA1与TMPRSS15，COMP、EDA2R、FCRL1、NOTCH1与TMPRSS15，AREG、COMP、EDA2R、TMPRSS15与TNC，COMP、EDA2R、FCRL1、NOTCH1与PTX3，COMP、EDA2R、FCRL1、GDF15与TMPRSS15，AREG、COMP、EDA2R、SERPINA1与TMPRSS15，AREG、COMP、EDA2R、GDF15与TMPRSS15，COMP、EDA2R、GDF15、NOTCH1与SERPINA1，FCRL1、GDF15、NOTCH1、PTX3与TMPRSS15，COMP、FCRL1、GDF15、TMPRSS15与TNC，CEACAM5、COMP、FCRL1、GDF15与PTX3，AREG、CEACAM5、GDF15、NOTCH1与PTX3，AREG、COMP、GDF15、PTX3与TMPRSS15，CEACAM5、COMP、EDA2R、PTX3与TMPRSS15，CEACAM5、GDF15、NOTCH1、PTX3与SERPINA1，CEACAM5、COMP、GDF15、SERPINA1与TMPRSS15，EDA2R、FCRL1、GDF15、PTX3与TMPRSS15，CEACAM5、COMP、GDF15、NOTCH1与TMPRSS15，CEACAM5、COMP、EDA2R、FCRL1与TMPRSS15，AREG、COMP、GDF15、NOTCH1与TMPRSS15，CEACAM5、COMP、GDF15、NOTCH1与SERPINA1，CEACAM5、COMP、EDA2R、FCRL1与PTX3，AREG、FCRL1、GDF15、NOTCH1与PTX3，AREG、COMP、EDA2R、NOTCH1与TMPRSS15，AREG、COMP、GDF15、TMPRSS15与TNC，FCRL1、GDF15、NOTCH1、PTX3与TNC，COMP、FCRL1、GDF15、PTX3与SERPINA1，FCRL1、GDF15、NOTCH1、PTX3与SERPINA1，CEACAM5、GDF15、NOTCH1、PTX3与TMPRSS15，EDA2R、GDF15、NOTCH1、PTX3与TNC，COMP、EDA2R、FCRL1、GDF15与NOTCH1，COMP、EDA2R、SERPINA1、TMPRSS15与TNC，COMP、EDA2R、GDF15、SERPINA1与TMPRSS15，FCRL1、GDF15、PTX3、TMPRSS15与TNC，COMP、GDF15、NOTCH1、SERPINA1与TNC，AREG、COMP、FCRL1、GDF15与NOTCH1，AREG、COMP、EDA2R、FCRL1与PTX3，COMP、GDF15、SERPINA1、TMPRSS15与TNC，AREG、COMP、GDF15、NOTCH1与SERPINA1，CEACAM5、EDA2R、GDF15、NOTCH1与PTX3，CEACAM5、COMP、EDA2R、GDF15与PTX3，CEACAM5、COMP、EDA2R、TMPRSS15与TNC，FCRL1、GDF15、NOTCH1、TMPRSS15与TNC，AREG、COMP、EDA2R、GDF15与PTX3，CEACAM5、COMP、EDA2R、FCRL1与SERPINA1，CEACAM5、GDF15、NOTCH1、SERPINA1与TNC，CEACAM5、COMP、FCRL1、GDF15与TMPRSS15，CEACAM5、COMP、FCRL1、GDF15与NOTCH1，COMP、EDA2R、FCRL1、PTX3与TNC，COMP、GDF15、PTX3、SERPINA1与TNC，COMP、FCRL1、GDF15、SERPINA1与TMPRSS15，AREG、FCRL1、GDF15、NOTCH1与TMPRSS15，CEACAM5、COMP、EDA2R、GDF15与TMPRSS15，COMP、EDA2R、FCRL1、PTX3与SERPINA1，AREG、COMP、FCRL1、GDF15与PTX3，COMP、EDA2R、NOTCH1、PTX3与TMPRSS15，COMP、EDA2R、GDF15、PTX3与TNC，COMP、EDA2R、FCRL1、NOTCH1与SERPINA1，AREG、EDA2R、GDF15、NOTCH1与PTX3，CEACAM5、COMP、EDA2R、PTX3与TNC，CEACAM5、COMP、FCRL1、GDF15与SERPINA1，AREG、COMP、GDF15、SERPINA1与TMPRSS15，AREG、GDF15、NOTCH1、PTX3与TNC，CEACAM5、COMP、EDA2R、FCRL1与TNC，GDF15、NOTCH1、PTX3、SERPINA1与TMPRSS15，COMP、EDA2R、NOTCH1、PTX3与SERPINA1，CEACAM5、FCRL1、GDF15、NOTCH1与PTX3，AREG、COMP、EDA2R、FCRL1与GDF15，COMP、EDA2R、FCRL1、GDF15与TNC，AREG、CEACAM5、GDF15、NOTCH1与TMPRSS15，AREG、CEACAM5、COMP、EDA2R与PTX3，FCRL1、GDF15、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、FCRL1、GDF15、PTX3与TMPRSS15，EDA2R、GDF15、NOTCH1、PTX3与TMPRSS15，CEACAM5、COMP、FCRL1、GDF15与TNC，COMP、GDF15、NOTCH1、SERPINA1与TMPRSS15，COMP、EDA2R、NOTCH1、TMPRSS15与TNC，CEACAM5、COMP、GDF15、SERPINA1与TNC，EDA2R、GDF15、NOTCH1、TMPRSS15与TNC，AREG、COMP、GDF15、NOTCH1与TNC，COMP、EDA2R、FCRL1、SERPINA1与TNC，AREG、COMP、EDA2R、FCRL1与NOTCH1，COMP、EDA2R、NOTCH1、PTX3与TNC，AREG、CEACAM5、COMP、EDA2R与FCRL1，COMP、FCRL1、PTX3、TMPRSS15与TNC，GDF15、NOTCH1、PTX3、SERPINA1与TNC，AREG、GDF15、NOTCH1、TMPRSS15与TNC，CEACAM5、FCRL1、GDF15、NOTCH1与TNC，CEACAM5、FCRL1、GDF15、NOTCH1与TMPRSS15，FCRL1、GDF15、NOTCH1、SERPINA1与TNC，AREG、COMP、FCRL1、GDF15与SERPINA1，CEACAM5、COMP、EDA2R、NOTCH1与PTX3，AREG、COMP、FCRL1、GDF15与TNC，CEACAM5、COMP、EDA2R、GDF15与TNC，COMP、EDA2R、GDF15、NOTCH1与TMPRSS15，AREG、EDA2R、FCRL1、PTX3与TMPRSS15，AREG、COMP、EDA2R、NOTCH1与PTX3，AREG、GDF15、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、COMP、GDF15与TNC，AREG、CEACAM5、COMP、PTX3与TMPRSS15，COMP、EDA2R、FCRL1、GDF15与SERPINA1，CEACAM5、COMP、EDA2R、GDF15与NOTCH1，CEACAM5、EDA2R、GDF15、TMPRSS15与TNC，COMP、EDA2R、GDF15、PTX3与SERPINA1，AREG、COMP、EDA2R、FCRL1与SERPINA1，CEACAM5、FCRL1、GDF15、TMPRSS15与TNC，AREG、FCRL1、GDF15、TMPRSS15与TNC，AREG、CEACAM5、COMP、EDA2R与GDF15，AREG、CEACAM5、COMP、FCRL1与GDF15，EDA2R、FCRL1、GDF15、TMPRSS15与TNC，COMP、EDA2R、GDF15、NOTCH1与TNC，EDA2R、GDF15、NOTCH1、PTX3与SERPINA1，CEACAM5、EDA2R、FCRL1、TMPRSS15与TNC，COMP、EDA2R、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、COMP、GDF15与SERPINA1，EDA2R、FCRL1、GDF15、NOTCH1与TMPRSS15，AREG、GDF15、NOTCH1、PTX3与TMPRSS15，COMP、FCRL1、GDF15、SERPINA1与TNC，EDA2R、FCRL1、GDF15、NOTCH1与PTX3，CEACAM5、COMP、FCRL1、PTX3与TMPRSS15，AREG、COMP、EDA2R、FCRL1与TNC，AREG、CEACAM5、COMP、TMPRSS15与TNC，AREG、CEACAM5、GDF15、NOTCH1与SERPINA1，CEACAM5、COMP、PTX3、TMPRSS15与TNC，FCRL1、GDF15、PTX3、SERPINA1与TMPRSS15，CEACAM5、COMP、EDA2R、FCRL1与GDF15，EDA2R、FCRL1、NOTCH1、TMPRSS15与TNC，CEACAM5、COMP、EDA2R、SERPINA1与TNC，AREG、CEACAM5、EDA2R、TMPRSS15与TNC，EDA2R、GDF15、PTX3、TMPRSS15与TNC，AREG、COMP、GDF15、PTX3与TNC，CEACAM5、EDA2R、FCRL1、GDF15与TMPRSS15，AREG、CEACAM5、EDA2R、PTX3与TMPRSS15，GDF15、NOTCH1、SERPINA1、TMPRSS15与TNC，AREG、GDF15、PTX3、TMPRSS15与TNC，AREG、EDA2R、GDF15、NOTCH1与TMPRSS15，CEACAM5、FCRL1、GDF15、NOTCH1与SERPINA1，CEACAM5、COMP、EDA2R、NOTCH1与SERPINA1，CEACAM5、COMP、EDA2R、PTX3与SERPINA1，AREG、EDA2R、GDF15、PTX3与TMPRSS15，AREG、EDA2R、FCRL1、TMPRSS15与TNC，COMP、EDA2R、NOTCH1、SERPINA1与TMPRSS15，EDA2R、FCRL1、SERPINA1、TMPRSS15与TNC，AREG、GDF15、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、EDA2R、NOTCH1、TMPRSS15与TNC，AREG、CEACAM5、EDA2R、FCRL1与TMPRSS15，CEACAM5、COMP、GDF15、PTX3与SERPINA1，AREG、COMP、EDA2R、PTX3与TNC，AREG、COMP、EDA2R、GDF15与NOTCH1，AREG、EDA2R、NOTCH1、TMPRSS15与TNC，AREG、EDA2R、FCRL1、NOTCH1与TMPRSS15，EDA2R、FCRL1、NOTCH1、PTX3与TMPRSS15，EDA2R、GDF15、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、EDA2R、FCRL1、PTX3与TMPRSS15，AREG、COMP、GDF15、PTX3与SERPINA1，CEACAM5、EDA2R、PTX3、TMPRSS15与TNC，CEACAM5、COMP、EDA2R、SERPINA1与TMPRSS15，AREG、COMP、FCRL1、PTX3与TMPRSS15，AREG、FCRL1、GDF15、PTX3与TMPRSS15，CEACAM5、EDA2R、GDF15、NOTCH1与TNC，CEACAM5、COMP、FCRL1、TMPRSS15与TNC，AREG、EDA2R、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、COMP、EDA2R、FCRL1与NOTCH1，CEACAM5、COMP、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、GDF15、TMPRSS15与TNC，CEACAM5、EDA2R、GDF15、NOTCH1与TMPRSS15，AREG、CEACAM5、FCRL1、GDF15与NOTCH1，AREG、EDA2R、GDF15、NOTCH1与SERPINA1，AREG、FCRL1、GDF15、NOTCH1与SERPINA1，CEACAM5、GDF15、PTX3、TMPRSS15与TNC，AREG、EDA2R、FCRL1、GDF15与TMPRSS15，AREG、EDA2R、NOTCH1、PTX3与TMPRSS15，AREG、COMP、EDA2R、PTX3与SERPINA1，AREG、COMP、PTX3、TMPRSS15与TNC，CEACAM5、EDA2R、GDF15、PTX3与TMPRSS15，CEACAM5、GDF15、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、GDF15、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、GDF15、NOTCH1与TNC，CEACAM5、EDA2R、GDF15、NOTCH1与SERPINA1，AREG、FCRL1、GDF15、NOTCH1与TNC，AREG、CEACAM5、EDA2R、NOTCH1与TMPRSS15，AREG、EDA2R、FCRL1、SERPINA1与TMPRSS15，AREG、EDA2R、PTX3、TMPRSS15与TNC，AREG、EDA2R、GDF15、TMPRSS15与TNC，AREG、CEACAM5、EDA2R、GDF15与TMPRSS15，AREG、COMP、FCRL1、TMPRSS15与TNC，EDA2R、GDF15、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、COMP、NOTCH1与PTX3，CEACAM5、COMP、EDA2R、GDF15与SERPINA1，EDA2R、FCRL1、GDF15、SERPINA1与TMPRSS15，AREG、CEACAM5、EDA2R、GDF15与NOTCH1，CEACAM5、COMP、FCRL1、PTX3与TNC，EDA2R、FCRL1、PTX3、SERPINA1与TMPRSS15，EDA2R、FCRL1、GDF15、NOTCH1与SERPINA1，AREG、CEACAM5、COMP、SERPINA1与TMPRSS15，CEACAM5、COMP、EDA2R、NOTCH1与TNC，AREG、CEACAM5、COMP、FCRL1与TMPRSS15，GDF15、PTX3、SERPINA1、TMPRSS15与TNC，CEACAM5、COMP、FCRL1、SERPINA1与TMPRSS15，CEACAM5、EDA2R、NOTCH1、PTX3与TNC，EDA2R、FCRL1、PTX3、TMPRSS15与TNC，AREG、CEACAM5、COMP、EDA2R与NOTCH1，FCRL1、GDF15、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、COMP、EDA2R与TNC，AREG、CEACAM5、FCRL1、TMPRSS15与TNC，CEACAM5、EDA2R、FCRL1、NOTCH1与TMPRSS15，AREG、COMP、GDF15、SERPINA1与TNC，CEACAM5、EDA2R、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、COMP、EDA2R与SERPINA1，CEACAM5、EDA2R、NOTCH1、SERPINA1与TMPRSS15，AREG、COMP、EDA2R、GDF15与TNC，AREG、CEACAM5、GDF15、PTX3与TMPRSS15，COMP、EDA2R、FCRL1、NOTCH1与TNC，COMP、EDA2R、NOTCH1、SERPINA1与TNC，CEACAM5、EDA2R、NOTCH1、PTX3与TMPRSS15，AREG、CEACAM5、NOTCH1、TMPRSS15与TNC，EDA2R、NOTCH1、PTX3、SERPINA1与TMPRSS15，AREG、COMP、EDA2R、GDF15与SERPINA1，AREG、CEACAM5、COMP、PTX3与TNC，AREG、GDF15、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、FCRL1、GDF15与TMPRSS15，CEACAM5、COMP、EDA2R、NOTCH1与TMPRSS15，COMP、NOTCH1、PTX3、TMPRSS15与TNC，CEACAM5、COMP、NOTCH1、PTX3与TNC，COMP、FCRL1、PTX3、SERPINA1与TMPRSS15，COMP、EDA2R、PTX3、SERPINA1与TNC，EDA2R、FCRL1、NOTCH1、SERPINA1与TMPRSS15，AREG、CEACAM5、COMP、FCRL1与PTX3，AREG、CEACAM5、COMP、NOTCH1与TMPRSS15，EDA2R、NOTCH1、PTX3、TMPRSS15与TNC，AREG、COMP、EDA2R、NOTCH1与SERPINA1，CEACAM5、FCRL1、GDF15、SERPINA1与TMPRSS15，EDA2R、FCRL1、GDF15、NOTCH1与TNC，COMP、FCRL1、SERPINA1、TMPRSS15与TNC，AREG、GDF15、NOTCH1、SERPINA1与TNC，EDA2R、NOTCH1、SERPINA1、TMPRSS15与TNC，CEACAM5、GDF15、PTX3、SERPINA1与TMPRSS15，CEACAM5、EDA2R、FCRL1、SERPINA1与TMPRSS15，AREG、CEACAM5、COMP、FCRL1与TNC，AREG、CEACAM5、EDA2R、SERPINA1与TMPRSS15，EDA2R、GDF15、SERPINA1、TMPRSS15与TNC，EDA2R、GDF15、NOTCH1、SERPINA1与TNC，CEACAM5、NOTCH1、PTX3、TMPRSS15与TNC，AREG、CEACAM5、PTX3、TMPRSS15与TNC，AREG、EDA2R、FCRL1、GDF15与NOTCH1，EDA2R、PTX3、SERPINA1、TMPRSS15与TNC，AREG、COMP、NOTCH1、PTX3与TMPRSS15，COMP、EDA2R、GDF15、SERPINA1与TNC，EDA2R、FCRL1、NOTCH1、PTX3与TNC，CEACAM5、COMP、PTX3、SERPINA1与TNC，COMP、FCRL1、NOTCH1、PTX3与TMPRSS15，CEACAM5、EDA2R、NOTCH1、PTX3与SERPINA1，CEACAM5、NOTCH1、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、EDA2R、NOTCH1与PTX3，AREG、COMP、EDA2R、NOTCH1与TNC，AREG、GDF15、SERPINA1、TMPRSS15与TNC，AREG、FCRL1、GDF15、SERPINA1与TMPRSS15，AREG、EDA2R、SERPINA1、TMPRSS15与TNC，CEACAM5、EDA2R、FCRL1、GDF15与NOTCH1，AREG、EDA2R、FCRL1、NOTCH1与PTX3，AREG、CEACAM5、COMP、NOTCH1与TNC，CEACAM5、FCRL1、PTX3、TMPRSS15与TNC，CEACAM5、EDA2R、FCRL1、NOTCH1与SERPINA1，CEACAM5、EDA2R、GDF15、SERPINA1与TMPRSS15，CEACAM5、COMP、PTX3、SERPINA1与TMPRSS15，AREG、FCRL1、PTX3、TMPRSS15与TNC，AREG、COMP、FCRL1、PTX3与TNC，CEACAM5、COMP、NOTCH1、PTX3与TMPRSS15，CEACAM5、EDA2R、FCRL1、NOTCH1与PTX3，AREG、EDA2R、GDF15、SERPINA1与TMPRSS15，CEACAM5、COMP、NOTCH1、SERPINA1与TNC，AREG、NOTCH1、PTX3、TMPRSS15与TNC，AREG、COMP、FCRL1、NOTCH1与TMPRSS15，CEACAM5、COMP、FCRL1、NOTCH1与TMPRSS15，CEACAM5、FCRL1、NOTCH1、TMPRSS15与TNC，AREG、COMP、SERPINA1、TMPRSS15与TNC，COMP、FCRL1、NOTCH1、PTX3与TNC，CEACAM5、FCRL1、NOTCH1、PTX3与TMPRSS15，COMP、FCRL1、NOTCH1、TMPRSS15与TNC，AREG、COMP、FCRL1、NOTCH1与PTX3，AREG、FCRL1、NOTCH1、PTX3与TMPRSS15，CEACAM5、COMP、FCRL1、NOTCH1与PTX3，CEACAM5、COMP、FCRL1、PTX3与SERPINA1，CEACAM5、COMP、FCRL1、SERPINA1与TNC，AREG、CEACAM5、FCRL1、PTX3与TMPRSS15，AREG、CEACAM5、SERPINA1、TMPRSS15与TNC，AREG、COMP、FCRL1、PTX3与SERPINA1，AREG、COMP、FCRL1、SERPINA1与TMPRSS15，COMP、PTX3、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、COMP、NOTCH1与SERPINA1，CEACAM5、EDA2R、PTX3、SERPINA1与TMPRSS15，AREG、EDA2R、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、EDA2R、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、NOTCH1与TNC，AREG、CEACAM5、COMP、FCRL1与SERPINA1，AREG、CEACAM5、COMP、FCRL1与NOTCH1，AREG、EDA2R、GDF15、NOTCH1与TNC，FCRL1、NOTCH1、PTX3、TMPRSS15与TNC，CEACAM5、EDA2R、FCRL1、NOTCH1与TNC，AREG、CEACAM5、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、COMP、PTX3与SERPINA1，CEACAM5、COMP、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、NOTCH1、PTX3与TMPRSS15，CEACAM5、PTX3、SERPINA1、TMPRSS15与TNC，AREG、EDA2R、NOTCH1、PTX3与TNC，EDA2R、FCRL1、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、FCRL1、NOTCH1与TMPRSS15，FCRL1、NOTCH1、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、NOTCH1、SERPINA1与TMPRSS15，FCRL1、PTX3、SERPINA1、TMPRSS15与TNC，AREG、COMP、EDA2R、SERPINA1与TNC，AREG、CEACAM5、GDF15、SERPINA1与TMPRSS15，AREG、FCRL1、NOTCH1、TMPRSS15与TNC，CEACAM5、NOTCH1、PTX3、SERPINA1与TMPRSS15，COMP、FCRL1、PTX3、SERPINA1与TNC，CEACAM5、COMP、NOTCH1、TMPRSS15与TNC，CEACAM5、COMP、NOTCH1、SERPINA1与TMPRSS15，AREG、CEACAM5、NOTCH1、PTX3与TNC，CEACAM5、EDA2R、NOTCH1、SERPINA1与TNC，AREG、CEACAM5、FCRL1、GDF15与PTX3，CEACAM5、COMP、FCRL1、NOTCH1与SERPINA1，CEACAM5、FCRL1、SERPINA1、TMPRSS15与TNC，AREG、EDA2R、NOTCH1、PTX3与SERPINA1，CEACAM5、FCRL1、PTX3、SERPINA1与TMPRSS15，AREG、FCRL1、GDF15、PTX3与TNC，AREG、COMP、NOTCH1、PTX3与TNC，CEACAM5、FCRL1、NOTCH1、SERPINA1与TMPRSS15，FCRL1、NOTCH1、SERPINA1、TMPRSS15与TNC，AREG、COMP、PTX3、SERPINA1与TMPRSS15，COMP、FCRL1、NOTCH1、PTX3与SERPINA1，AREG、EDA2R、FCRL1、GDF15与PTX3，AREG、FCRL1、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、FCRL1、NOTCH1与PTX3，CEACAM5、NOTCH1、PTX3、SERPINA1与TNC，AREG、EDA2R、FCRL1、NOTCH1与SERPINA1，NOTCH1、PTX3、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、EDA2R、NOTCH1与TNC，EDA2R、FCRL1、GDF15、PTX3与TNC，CEACAM5、EDA2R、FCRL1、GDF15与PTX3，CEACAM5、FCRL1、GDF15、PTX3与TNC，COMP、NOTCH1、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、EDA2R、FCRL1与NOTCH1，AREG、NOTCH1、PTX3、SERPINA1与TMPRSS15，AREG、FCRL1、PTX3、SERPINA1与TMPRSS15，AREG、CEACAM5、EDA2R、GDF15与PTX3，AREG、COMP、NOTCH1、TMPRSS15与TNC，AREG、PTX3、SERPINA1、TMPRSS15与TNC，AREG、CEACAM5、FCRL1、SERPINA1与TMPRSS15，AREG、NOTCH1、SERPINA1、TMPRSS15与TNC，COMP、FCRL1、NOTCH1、SERPINA1与TNC，AREG、CEACAM5、COMP、SERPINA1与TNC，FCRL1、GDF15、PTX3、SERPINA1与TNC，CEACAM5、EDA2R、GDF15、PTX3与TNC，AREG、CEACAM5、NOTCH1、SERPINA1与TNC，COMP、NOTCH1、PTX3、SERPINA1与TNC，CEACAM5、GDF15、PTX3、SERPINA1与TNC，AREG、COMP、FCRL1、NOTCH1与TNC，EDA2R、FCRL1、GDF15、PTX3与SERPINA1，AREG、COMP、NOTCH1、SERPINA1与TMPRSS15，COMP、NOTCH1、SERPINA1、TMPRSS15与TNC，EDA2R、FCRL1、NOTCH1、SERPINA1与TNC，AREG、FCRL1、GDF15、PTX3与SERPINA1，CEACAM5、FCRL1、NOTCH1、PTX3与TNC，AREG、FCRL1、NOTCH1、PTX3与TNC，AREG、EDA2R、FCRL1、PTX3与SERPINA1，AREG、FCRL1、NOTCH1、PTX3与SERPINA1，AREG、FCRL1、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、EDA2R、GDF15、PTX3与SERPINA1，EDA2R、NOTCH1、PTX3、SERPINA1与TNC，AREG、CEACAM5、EDA2R、FCRL1与PTX3，AREG、COMP、FCRL1、NOTCH1与SERPINA1，CEACAM5、FCRL1、GDF15、PTX3与SERPINA1，AREG、EDA2R、FCRL1、NOTCH1与TNC，EDA2R、FCRL1、PTX3、SERPINA1与TNC，FCRL1、NOTCH1、PTX3、SERPINA1与TNC，AREG、CEACAM5、GDF15、PTX3与TNC，AREG、COMP、FCRL1、SERPINA1与TNC，COMP、FCRL1、NOTCH1、SERPINA1与TMPRSS15，CEACAM5、FCRL1、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、GDF15、PTX3与SERPINA1，AREG、COMP、NOTCH1、PTX3与SERPINA1，AREG、CEACAM5、FCRL1、GDF15与TNC，AREG、CEACAM5、FCRL1、NOTCH1与TNC，AREG、EDA2R、FCRL1、PTX3与TNC，AREG、COMP、PTX3、SERPINA1与TNC，CEACAM5、EDA2R、FCRL1、PTX3与TNC，CEACAM5、FCRL1、NOTCH1、SERPINA1与TNC，AREG、COMP、NOTCH1、SERPINA1与TNC，CEACAM5、FCRL1、PTX3、SERPINA1与TNC，CEACAM5、EDA2R、FCRL1、PTX3与SERPINA1，AREG、EDA2R、NOTCH1、SERPINA1与TNC，AREG、FCRL1、NOTCH1、SERPINA1与TNC，AREG、CEACAM5、FCRL1、NOTCH1与SERPINA1，AREG、NOTCH1、PTX3、SERPINA1与TNC，CEACAM5、FCRL1、GDF15、SERPINA1与TNC，CEACAM5、EDA2R、FCRL1、GDF15与TNC，AREG、CEACAM5、FCRL1、PTX3与TNC，AREG、FCRL1、GDF15、SERPINA1与TNC，AREG、EDA2R、GDF15、PTX3与TNC，EDA2R、GDF15、PTX3、SERPINA1与TNC，AREG、CEACAM5、EDA2R、FCRL1与GDF15，AREG、GDF15、PTX3、SERPINA1与TNC，AREG、EDA2R、FCRL1、GDF15与SERPINA1，AREG、CEACAM5、FCRL1、GDF15与SERPINA1，AREG、EDA2R、GDF15、PTX3与SERPINA1，AREG、CEACAM5、FCRL1、PTX3与SERPINA1，CEACAM5、EDA2R、PTX3、SERPINA1与TNC，AREG、EDA2R、FCRL1、GDF15与TNC，EDA2R、FCRL1、GDF15、SERPINA1与TNC，AREG、CEACAM5、EDA2R、PTX3与TNC，CEACAM5、EDA2R、GDF15、SERPINA1与TNC，CEACAM5、EDA2R、FCRL1、SERPINA1与TNC，CEACAM5、EDA2R、FCRL1、GDF15与SERPINA1，AREG、FCRL1、PTX3、SERPINA1与TNC，AREG、CEACAM5、EDA2R、PTX3与SERPINA1，AREG、CEACAM5、EDA2R、GDF15与TNC，AREG、CEACAM5、EDA2R、FCRL1与SERPINA1，AREG、CEACAM5、EDA2R、FCRL1与TNC，AREG、CEACAM5、GDF15、SERPINA1与TNC，AREG、CEACAM5、EDA2R、GDF15与SERPINA1，AREG、CEACAM5、PTX3、SERPINA1与TNC，AREG、EDA2R、FCRL1、SERPINA1与TNC，AREG、CEACAM5、FCRL1、SERPINA1与TNC，AREG、CEACAM5、EDA2R、SERPINA1与TNC，AREG、EDA2R、PTX3、SERPINA1与TNC，或AREG、EDA2R、GDF15、SERPINA1与TNC；进一步为COMP、FCRL1、GDF15、NOTCH1与PTX3。Preferably, the 5 markers combination is: COMP, GDF15, NOTCH1, PTX3 and TMPRSS15, COMP, FCRL1, GDF15, NOTCH1 and PTX3, COMP, GDF15, NOTCH1, PTX3 and TNC, COMP, EDA2R, GDF15, NOTCH1 and PTX3, CEACAM5, COMP, GDF15, NOTCH1 and PTX3, COMP, FCRL1, GDF15, PTX3 and TMPRSS15, COMP, EDA2R, GDF15, PTX3 and TMPRSS15, CO MP, GDF15, PTX3, TMPRSS15 and TNC, COMP, GDF15, NOTCH1, TMPRSS15 and TNC, COMP, EDA2R, FCRL1, PTX3 and TMPRSS15, CEACAM5, COMP, GDF15, PTX3 and TNC, AREG, CEACAM5, COMP, GDF15 and NOTCH1, COMP, EDA2R, FCRL1, TMPRSS15 and TNC, COMP, EDA2R, PTX3, TMPRSS15 and TNC, CEACAM5, GDF15, NOTCH1, PTX 3 and TNC, COMP, GDF15, NOTCH1, PTX3 and SERPINA1, AREG, COMP, FCRL1, GDF15 and TMPRSS15, CEACAM5, COMP, GDF15, NOTCH1 and TNC, AREG, COMP, EDA2R, PTX3 and TMPRSS15, CEACAM5, COMP, GDF15, PTX3 and TMPRSS15, GDF15, NOTCH1, PTX3, TMPRSS15 and TNC, AREG, COMP, GDF15, NOTCH1 and PTX3, CEACAM5, G DF15, NOTCH1, TMPRSS15 and TNC, CEACAM5, COMP, GDF15, TMPRSS15 and TNC, AREG, COMP, EDA2R, FCRL1 and TMPRSS15, COMP, FCRL1, GDF15, PTX3 and TNC, AREG, CEACAM5, COMP, EDA2R and TMPRSS15, COMP, FCRL1, GDF15, NOTCH1 and TMPRSS15, AREG, CEACAM5, COMP, GDF15 and PTX3, AREG, CEACAM5, COMP, GDF1 5 and TMPRSS15, COMP, EDA2R, FCRL1, GDF15 and PTX3, COMP, FCRL1, GDF15, NOTCH1 and SERPINA1, COMP, EDA2R, FCRL1, SERPINA1 and TMPRSS15, COMP, EDA2R, GDF15, TMPRSS15 and TNC, COMP, FCRL1, GDF15, NOTCH1 and TNC, COMP, GDF15, PTX3, SERPINA1 and TMPRSS15, COMP, EDA2R, FCRL1, NOTCH1 and TMPRSS1 5, AREG, COMP, EDA2R, TMPRSS15 and TNC, COMP, EDA2R, FCRL1, NOTCH1 and PTX3, COMP, EDA2R, FCRL1, GDF15 and TMPRSS15, AREG, COMP, EDA2R, SERPINA1 and TMPRSS15, AREG, COMP, EDA2R, GDF15 and TMPRSS15, COMP, EDA2R, GDF15, NOTCH1 and SERPINA1, FCRL1, GDF15, NOTCH1, PTX3 and TMPRSS15, COMP, FCR L1, GDF15, TMPRSS15 and TNC, CEACAM5, COMP, FCRL1, GDF15 and PTX3, AREG, CEACAM5, GDF15, NOTCH1 and PTX3, AREG, COMP, GDF15, PTX3 and TMPRSS15, CEACAM5, COMP, EDA2R, PTX3 and TMPRSS15, CEACAM5, GDF15, NOTCH1, PTX3 and SERPINA1, CEACAM5, COMP, GDF15, SERPINA1 and TMPRSS15, EDA2R, FCRL1, GDF15, PTX3 and TMPRSS15, CEACAM5, COMP, GDF15, NOTCH1 and TMPRSS15, CEACAM5, COMP, EDA2R, FCRL1 and TMPRSS15, AREG, COMP, GDF15, NOTCH1 and TMPRSS15, CEACAM5, COMP, GDF15, NOTCH1 and SERPINA1, CEACAM5, COMP, EDA2R, FCRL1 and PTX3, AREG, FCRL1, GDF15, NOTCH1 and PTX3, AREG, COMP, EDA2R, NOTCH1 and TMPRSS15, AREG, COMP, GDF15, TMPRSS15 and TNC, FCRL1, GDF15, NOTCH1, PTX3 and TNC, COMP, FCRL1, GDF15, PTX3 and SERPINA1, FCRL1, GDF15, NOTCH1, PTX3 and SERPINA1, CEACAM5, GDF15, NOTCH1, PTX3 and TMPRSS15, EDA2R, GDF15, NOTCH1, PTX3 and TNC, COMP, EDA2R, FCRL1, GDF15 and NOTCH1, COMP, EDA2R, SERPINA1, TMPRSS15, and TNC, COMP, EDA2R, GDF15, SERPINA1, and TMPRSS15, FCRL1, GDF15, PTX3, TMPRSS15, and TNC, COMP, GDF15, NOTCH1, SERPINA1, and TNC, AREG, COMP, FCRL1, GDF15, and NOTCH1, AREG, COMP, EDA2R, FCRL1, and PTX3, COMP, GDF15, SERPINA1, TMPRSS15, and TNC, AREG, COMP, GDF 15, NOTCH1 and SERPINA1, CEACAM5, EDA2R, GDF15, NOTCH1 and PTX3, CEACAM5, COMP, EDA2R, GDF15 and PTX3, CEACAM5, COMP, EDA2R, TMPRSS15 and TNC, FCRL1, GDF15, NOTCH1, TMPRSS15 and TNC, AREG, COMP, EDA2R, GDF15 and PTX3, CEACAM5, COMP, EDA2R, FCRL1 and SERPINA1, CEACAM5, GDF15, NOTCH1, SER PINA1 and TNC, CEACAM5, COMP, FCRL1, GDF15 and TMPRSS15, CEACAM5, COMP, FCRL1, GDF15 and NOTCH1, COMP, EDA2R, FCRL1, PTX3 and TNC, COMP, GDF15, PTX3, SERPINA1 and TNC, COMP, FCRL1, GDF15, SERPINA1 and TMPRSS15, AREG, FCRL1, GDF15, NOTCH1 and TMPRSS15, CEACAM5, COMP, EDA2R, GDF15 and TMPRSS1 5, COMP, EDA2R, FCRL1, PTX3 and SERPINA1, AREG, COMP, FCRL1, GDF15 and PTX3, COMP, EDA2R, NOTCH1, PTX3 and TMPRSS15, COMP, EDA2R, GDF15, PTX3 and TNC, COMP, EDA2R, FCRL1, NOTCH1 and SERPINA1, AREG, EDA2R, GDF15, NOTCH1 and PTX3, CEACAM5, COMP, EDA2R, PTX3 and TNC, CEACAM5, COMP, FCRL1, GDF 15 and SERPINA1, AREG, COMP, GDF15, SERPINA1 and TMPRSS15, AREG, GDF15, NOTCH1, PTX3 and TNC, CEACAM5, COMP, EDA2R, FCRL1 and TNC, GDF15, NOTCH1, PTX3, SERPINA1 and TMPRSS15, COMP, EDA2R, NOTCH1, PTX3 and SERPINA1, CEACAM5, FCRL1, GDF15, NOTCH1 and PTX3, AREG, COMP, EDA2R, FCRL1 and GDF15, C OMP, EDA2R, FCRL1, GDF15, and TNC, AREG, CEACAM5, GDF15, NOTCH1, and TMPRSS15, AREG, CEACAM5, COMP, EDA2R, and PTX3, FCRL1, GDF15, NOTCH1, SERPINA1, and TMPRSS15, CEACAM5, FCRL1, GDF15, PTX3, and TMPRSS15, EDA2R, GDF15, NOTCH1, PTX3, and TMPRSS15, CEACAM5, COMP, FCRL1, GDF15, and TNC, COMP, GD F15, NOTCH1, SERPINA1 and TMPRSS15, COMP, EDA2R, NOTCH1, TMPRSS15 and TNC, CEACAM5, COMP, GDF15, SERPINA1 and TNC, EDA2R, GDF15, NOTCH1, TMPRSS15 and TNC, AREG, COMP, GDF15, NOTCH1 and TNC, COMP, EDA2R, FCRL1, SERPINA1 and TNC, AREG, COMP, EDA2R, FCRL1 and NOTCH1, COMP, EDA2R, NOTCH1, PTX 3 and TNC, AREG, CEACAM5, COMP, EDA2R and FCRL1, COMP, FCRL1, PTX3, TMPRSS15 and TNC, GDF15, NOTCH1, PTX3, SERPINA1 and TNC, AREG, GDF15, NOTCH1, TMPRSS15 and TNC, CEACAM5, FCRL1, GDF15, NOTCH1 and TNC, CEACAM5, FCRL1, GDF15, NOTCH1 and TMPRSS15, FCRL1, GDF15, NOTCH1, SERPINA1 and TNC, AREG , COMP, FCRL1, GDF15, and SERPINA1, CEACAM5, COMP, EDA2R, NOTCH1, and PTX3, AREG, COMP, FCRL1, GDF15, and TNC, CEACAM5, COMP, EDA2R, GDF15, and TNC, COMP, EDA2R, GDF15, NOTCH1, and TMPRSS15, AREG, EDA2R, FCRL1, PTX3, and TMPRSS15, AREG, COMP, EDA2R, NOTCH1, and PTX3, AREG, GDF15, NOTCH1, PTX3, and SER PINA1, AREG, CEACAM5, COMP, GDF15, and TNC, AREG, CEACAM5, COMP, PTX3, and TMPRSS15, COMP, EDA2R, FCRL1, GDF15, and SERPINA1, CEACAM5, COMP, EDA2R, GDF15, and NOTCH1, CEACAM5, EDA2R, GDF15, TMPRSS15, and TNC, COMP, EDA2R, GDF15, PTX3, and SERPINA1, AREG, COMP, EDA2R, FCRL1, and SERPINA1, CEACA M5, FCRL1, GDF15, TMPRSS15 and TNC, AREG, FCRL1, GDF15, TMPRSS15 and TNC, AREG, CEACAM5, COMP, EDA2R and GDF15, AREG, CEACAM5, COMP, FCRL1 and GDF15, EDA2R, FCRL1, GDF15, TMPRSS15 and TNC, COMP, EDA2R, GDF15, NOTCH1 and TNC, EDA2R, GDF15, NOTCH1, PTX3 and SERPINA1, CEACAM5, EDA2R, FCRL1, T MPRSS15 and TNC, COMP, EDA2R, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, COMP, GDF15 and SERPINA1, EDA2R, FCRL1, GDF15, NOTCH1 and TMPRSS15, AREG, GDF15, NOTCH1, PTX3 and TMPRSS15, COMP, FCRL1, GDF15, SERPINA1 and TNC, EDA2R, FCRL1, GDF15, NOTCH1 and PTX3, CEACAM5, COMP, FCRL1, PTX3 and T MPRSS15, AREG, COMP, EDA2R, FCRL1 and TNC, AREG, CEACAM5, COMP, TMPRSS15 and TNC, AREG, CEACAM5, GDF15, NOTCH1 and SERPINA1, CEACAM5, COMP, PTX3, TMPRSS15 and TNC, FCRL1, GDF15, PTX3, SERPINA1 and TMPRSS15, CEACAM5, COMP, EDA2R, FCRL1 and GDF15, EDA2R, FCRL1, NOTCH1, TMPRSS15 and TNC, CE ACAM5, COMP, EDA2R, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, TMPRSS15 and TNC, EDA2R, GDF15, PTX3, TMPRSS15 and TNC, AREG, COMP, GDF15, PTX3 and TNC, CEACAM5, EDA2R, FCRL1, GDF15 and TMPRSS15, AREG, CEACAM5, EDA2R, PTX3 and TMPRSS15, GDF15, NOTCH1, SERPINA1, TMPRSS15 and TNC, AREG, GDF15 , PTX3, TMPRSS15, and TNC, AREG, EDA2R, GDF15, NOTCH1, and TMPRSS15, CEACAM5, FCRL1, GDF15, NOTCH1, and SERPINA1, CEACAM5, COMP, EDA2R, NOTCH1, and SERPINA1, CEACAM5, COMP, EDA2R, PTX3, and SERPINA1, AREG, EDA2R, GDF15, PTX3, and TMPRSS15, AREG, EDA2R, FCRL1, TMPRSS15, and TNC, COMP, EDA2R, NOT CH1, SERPINA1 and TMPRSS15, EDA2R, FCRL1, SERPINA1, TMPRSS15 and TNC, AREG, GDF15, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, EDA2R, NOTCH1, TMPRSS15 and TNC, AREG, CEACAM5, EDA2R, FCRL1 and TMPRSS15, CEACAM5, COMP, GDF15, PTX3 and SERPINA1, AREG, COMP, EDA2R, PTX3 and TNC, AREG, COMP, ED A2R, GDF15 and NOTCH1, AREG, EDA2R, NOTCH1, TMPRSS15 and TNC, AREG, EDA2R, FCRL1, NOTCH1 and TMPRSS15, EDA2R, FCRL1, NOTCH1, PTX3 and TMPRSS15, EDA2R, GDF15, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, EDA2R, FCRL1, PTX3 and TMPRSS15, AREG, COMP, GDF15, PTX3 and SERPINA1, CEACAM5, EDA2R, PT X3, TMPRSS15 and TNC, CEACAM5, COMP, EDA2R, SERPINA1 and TMPRSS15, AREG, COMP, FCRL1, PTX3 and TMPRSS15, AREG, FCRL1, GDF15, PTX3 and TMPRSS15, CEACAM5, EDA2R, GDF15, NOTCH1 and TNC, CEACAM5, COMP, FCRL1, TMPRSS15 and TNC, AREG, EDA2R, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, COMP, EDA2 R, FCRL1 and NOTCH1, CEACAM5, COMP, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, GDF15, TMPRSS15 and TNC, CEACAM5, EDA2R, GDF15, NOTCH1 and TMPRSS15, AREG, CEACAM5, FCRL1, GDF15 and NOTCH1, AREG, EDA2R, GDF15, NOTCH1 and SERPINA1, AREG, FCRL1, GDF15, NOTCH1 and SERPINA1, CEACAM5, GDF15, P TX3, TMPRSS15 and TNC, AREG, EDA2R, FCRL1, GDF15 and TMPRSS15, AREG, EDA2R, NOTCH1, PTX3 and TMPRSS15, AREG, COMP, EDA2R, PTX3 and SERPINA1, AREG, COMP, PTX3, TMPRSS15 and TNC, CEACAM5, EDA2R, GDF15, PTX3 and TMPRSS15, CEACAM5, GDF15, NOTCH1, SERPINA1 and TMPRSS15, CEACAM5, GDF15, SERP INA1, TMPRSS15 and TNC, AREG, CEACAM5, GDF15, NOTCH1 and TNC, CEACAM5, EDA2R, GDF15, NOTCH1 and SERPINA1, AREG, FCRL1, GDF15, NOTCH1 and TNC, AREG, CEACAM5, EDA2R, NOTCH1 and TMPRSS15, AREG, EDA2R, FCRL1, SERPINA1 and TMPRSS15, AREG, EDA2R, PTX3, TMPRSS15 and TNC, AREG, EDA2R, GDF15, TMP RSS15 and TNC, AREG, CEACAM5, EDA2R, GDF15 and TMPRSS15, AREG, COMP, FCRL1, TMPRSS15 and TNC, EDA2R, GDF15, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, COMP, NOTCH1 and PTX3, CEACAM5, COMP, EDA2R, GDF15 and SERPINA1, EDA2R, FCRL1, GDF15, SERPINA1 and TMPRSS15, AREG, CEACAM5, EDA2R, GDF 15 and NOTCH1, CEACAM5, COMP, FCRL1, PTX3 and TNC, EDA2R, FCRL1, PTX3, SERPINA1 and TMPRSS15, EDA2R, FCRL1, GDF15, NOTCH1 and SERPINA1, AREG, CEACAM5, COMP, SERPINA1 and TMPRSS15, CEACAM5, COMP, EDA2R, NOTCH1 and TNC, AREG, CEACAM5, COMP, FCRL1 and TMPRSS15, GDF15, PTX3, SERPINA1, TMPRS S15 and TNC, CEACAM5, COMP, FCRL1, SERPINA1 and TMPRSS15, CEACAM5, EDA2R, NOTCH1, PTX3 and TNC, EDA2R, FCRL1, PTX3, TMPRSS15 and TNC, AREG, CEACAM5, COMP, EDA2R and NOTCH1, FCRL1, GDF15, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, COMP, EDA2R and TNC, AREG, CEACAM5, FCRL1, TMPRSS15 and TNC, CEACAM5, EDA2R, FCRL1, NOTCH1 and TMPRSS15, AREG, COMP, GDF15, SERPINA1 and TNC, CEACAM5, EDA2R, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, COMP, EDA2R and SERPINA1, CEACAM5, EDA2R, NOTCH1, SERPINA1 and TMPRSS15, AREG, COMP, EDA2R, GDF15 and TNC, AREG, CEACAM5, GDF15, PTX3 and TMPRSS15 , COMP, EDA2R, FCRL1, NOTCH1 and TNC, COMP, EDA2R, NOTCH1, SERPINA1 and TNC, CEACAM5, EDA2R, NOTCH1, PTX3 and TMPRSS15, AREG, CEACAM5, NOTCH1, TMPRSS15 and TNC, EDA2R, NOTCH1, PTX3, SERPINA1 and TMPRSS15, AREG, COMP, EDA2R, GDF15 and SERPINA1, AREG, CEACAM5, COMP, PTX3 and TNC, AREG, GDF 15, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, FCRL1, GDF15 and TMPRSS15, CEACAM5, COMP, EDA2R, NOTCH1 and TMPRSS15, COMP, NOTCH1, PTX3, TMPRSS15 and TNC, CEACAM5, COMP, NOTCH1, PTX3 and TNC, COMP, FCRL1, PTX3, SERPINA1 and TMPRSS15, COMP, EDA2R, PTX3, SERPINA1 and TNC, EDA2R, FCRL1, NO TCH1, SERPINA1 and TMPRSS15, AREG, CEACAM5, COMP, FCRL1 and PTX3, AREG, CEACAM5, COMP, NOTCH1 and TMPRSS15, EDA2R, NOTCH1, PTX3, TMPRSS15 and TNC, AREG, COMP, EDA2R, NOTCH1 and SERPINA1, CEACAM5, FCRL1, GDF15, SERPINA1 and TMPRSS15, EDA2R, FCRL1, GDF15, NOTCH1 and TNC, COMP, FCRL1, SER PINA1, TMPRSS15 and TNC, AREG, GDF15, NOTCH1, SERPINA1 and TNC, EDA2R, NOTCH1, SERPINA1, TMPRSS15 and TNC, CEACAM5, GDF15, PTX3, SERPINA1 and TMPRSS15, CEACAM5, EDA2R, FCRL1, SERPINA1 and TMPRSS15, AREG, CEACAM5, COMP, FCRL1 and TNC, AREG, CEACAM5, EDA2R, SERPINA1 and TMPRSS15, EDA2R, GDF15, SERPINA1, TMPRSS15 and TNC, EDA2R, GDF15, NOTCH1, SERPINA1 and TNC, CEACAM5, NOTCH1, PTX3, TMPRSS15 and TNC, AREG, CEACAM5, PTX3, TMPRSS15 and TNC, AREG, EDA2R, FCRL1, GDF15 and NOTCH1, EDA2R, PTX3, SERPINA1, TMPRSS15 and TNC, AREG, COMP, NOTCH1, PTX3 and TMPRSS15, COMP, EDA2R, G DF15, SERPINA1 and TNC, EDA2R, FCRL1, NOTCH1, PTX3 and TNC, CEACAM5, COMP, PTX3, SERPINA1 and TNC, COMP, FCRL1, NOTCH1, PTX3 and TMPRSS15, CEACAM5, EDA2R, NOTCH1, PTX3 and SERPINA1, CEACAM5, NOTCH1, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, EDA2R, NOTCH1 and PTX3, AREG, COMP, EDA2R, NOT CH1 and TNC, AREG, GDF15, SERPINA1, TMPRSS15 and TNC, AREG, FCRL1, GDF15, SERPINA1 and TMPRSS15, AREG, EDA2R, SERPINA1, TMPRSS15 and TNC, CEACAM5, EDA2R, FCRL1, GDF15 and NOTCH1, AREG, EDA2R, FCRL1, NOTCH1 and PTX3, AREG, CEACAM5, COMP, NOTCH1 and TNC, CEACAM5, FCRL1, PTX3, TMPRSS15 and TN C, CEACAM5, EDA2R, FCRL1, NOTCH1 and SERPINA1, CEACAM5, EDA2R, GDF15, SERPINA1 and TMPRSS15, CEACAM5, COMP, PTX3, SERPINA1 and TMPRSS15, AREG, FCRL1, PTX3, TMPRSS15 and TNC, AREG, COMP, FCRL1, PTX3 and TNC, CEACAM5, COMP, NOTCH1, PTX3 and TMPRSS15, CEACAM5, EDA2R, FCRL1, NOTCH1 and PTX3 , AREG, EDA2R, GDF15, SERPINA1 and TMPRSS15, CEACAM5, COMP, NOTCH1, SERPINA1 and TNC, AREG, NOTCH1, PTX3, TMPRSS15 and TNC, AREG, COMP, FCRL1, NOTCH1 and TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1 and TMPRSS15, CEACAM5, FCRL1, NOTCH1, TMPRSS15 and TNC, AREG, COMP, SERPINA1, TMPRSS15 and TN C, COMP, FCRL1, NOTCH1, PTX3 and TNC, CEACAM5, FCRL1, NOTCH1, PTX3 and TMPRSS15, COMP, FCRL1, NOTCH1, TMPRSS15 and TNC, AREG, COMP, FCRL1, NOTCH1 and PTX3, AREG, FCRL1, NOTCH1, PTX3 and TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1 and PTX3, CEACAM5, COMP, FCRL1, PTX3 and SERPINA1, CEACAM5, COMP , FCRL1, SERPINA1 and TNC, AREG, CEACAM5, FCRL1, PTX3 and TMPRSS15, AREG, CEACAM5, SERPINA1, TMPRSS15 and TNC, AREG, COMP, FCRL1, PTX3 and SERPINA1, AREG, COMP, FCRL1, SERPINA1 and TMPRSS15, COMP, PTX3, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, COMP, NOTCH1 and SERPINA1, CEACAM5, EDA2 R, PTX3, SERPINA1 and TMPRSS15, AREG, EDA2R, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, EDA2R, NOTCH1 and SERPINA1, CEACAM5, COMP, FCRL1, NOTCH1 and TNC, AREG, CEACAM5, COMP, FCRL1 and SERPINA1, AREG, CEACAM5, COMP, FCRL1 and NOTCH1, AREG, EDA2R, GDF15, NOTCH1 and TNC, FCRL1, NOTCH1, PT X3, TMPRSS15 and TNC, CEACAM5, EDA2R, FCRL1, NOTCH1 and TNC, AREG, CEACAM5, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, COMP, PTX3 and SERPINA1, CEACAM5, COMP, NOTCH1, PTX3 and SERPINA1, AREG, CEACAM5, NOTCH1, PTX3 and TMPRSS15, CEACAM5, PTX3, SERPINA1, TMPRSS15 and TNC, AREG, EDA2R, N OTCH1, PTX3 and TNC, EDA2R, FCRL1, NOTCH1, PTX3 and SERPINA1, AREG, CEACAM5, NOTCH1, PTX3 and SERPINA1, AREG, CEACAM5, FCRL1, NOTCH1 and TMPRSS15, FCRL1, NOTCH1, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, NOTCH1, SERPINA1 and TMPRSS15, FCRL1, PTX3, SERPINA1, TMPRSS15 and TNC, AREG, CO MP, EDA2R, SERPINA1 and TNC, AREG, CEACAM5, GDF15, SERPINA1 and TMPRSS15, AREG, FCRL1, NOTCH1, TMPRSS15 and TNC, CEACAM5, NOTCH1, PTX3, SERPINA1 and TMPRSS15, COMP, FCRL1, PTX3, SERPINA1 and TNC, CEACAM5, COMP, NOTCH1, TMPRSS15 and TNC, CEACAM5, COMP, NOTCH1, SERPINA1 and TMPRSS15, AR EG, CEACAM5, NOTCH1, PTX3, and TNC, CEACAM5, EDA2R, NOTCH1, SERPINA1, and TNC, AREG, CEACAM5, FCRL1, GDF15, and PTX3, CEACAM5, COMP, FCRL1, NOTCH1, and SERPINA1, CEACAM5, FCRL1, SERPINA1, TMPRSS15, and TNC, AREG, EDA2R, NOTCH1, PTX3, and SERPINA1, CEACAM5, FCRL1, PTX3, SERPINA1, and TMPRSS15, AREG, FCRL1, GDF15, PTX3, and TNC, AREG, COMP, NOTCH1, PTX3, and TNC, CEACAM5, FCRL1, NOTCH1, SERPINA1, and TMPRSS15, FCRL1, NOTCH1, SERPINA1, and TMPRSS15, COMP, FCRL1, NOTCH1, PTX3, and SERPINA1, AREG, EDA2R, FCRL1, GDF15, and PTX3, AREG, FCRL1, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, FCRL1, NOTCH1 and PTX3, CEACAM5, NOTCH1, PTX3, SERPINA1 and TNC, AREG, EDA2R, FCRL1, NOTCH1 and SERPINA1, NOTCH1, PTX3, SERPINA1, TMPRSS15 and TNC, AREG, CEACAM5, EDA2R, NOTCH1 and TNC, EDA2R, FCRL1, GDF15, PTX3 and TNC, CEACAM5, EDA2R, FCRL1, G DF15 and PTX3, CEACAM5, FCRL1, GDF15, PTX3 and TNC, COMP, NOTCH1, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, EDA2R, FCRL1 and NOTCH1, AREG, NOTCH1, PTX3, SERPINA1 and TMPRSS15, AREG, FCRL1, PTX3, SERPINA1 and TMPRSS15, AREG, CEACAM5, EDA2R, GDF15 and PTX3, AREG, COMP, NOTCH1, TMPRSS15 with TNC, AREG, PTX3, SERPINA1, TMPRSS15 with TNC, AREG, CEACAM5, FCRL1, SERPINA1 with TMPRSS15, AREG, NOTCH1, SERPINA1, TMPRSS15 with TNC, COMP, FCRL1, NOTCH1, SERPINA1 with TNC, AREG, CEACAM5, COMP, SERPINA1 with TNC, FCRL1, GDF15, PTX3, SERPINA1 with TNC, CEACAM5, EDA2R, GDF15, PTX3 with TNC, AR EG, CEACAM5, NOTCH1, SERPINA1 and TNC, COMP, NOTCH1, PTX3, SERPINA1 and TNC, CEACAM5, GDF15, PTX3, SERPINA1 and TNC, AREG, COMP, FCRL1, NOTCH1 and TNC, EDA2R, FCRL1, GDF15, PTX3 and SERPINA1, AREG, COMP, NOTCH1, SERPINA1 and TMPRSS15, COMP, NOTCH1, SERPINA1, TMPRSS15 and TNC, EDA2R, FCR L1, NOTCH1, SERPINA1, and TNC, AREG, FCRL1, GDF15, PTX3, and SERPINA1, CEACAM5, FCRL1, NOTCH1, PTX3, and TNC, AREG, FCRL1, NOTCH1, PTX3, and TNC, AREG, EDA2R, FCRL1, PTX3, and SERPINA1, AREG, FCRL1, NOTCH1, PTX3, and SERPINA1, AREG, FCRL1, NOTCH1, PTX3, and SERPINA1, and TMPRSS15, CEACAM5, EDA2R, GDF15, P TX3 and SERPINA1, EDA2R, NOTCH1, PTX3, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, FCRL1 and PTX3, AREG, COMP, FCRL1, NOTCH1 and SERPINA1, CEACAM5, FCRL1, GDF15, PTX3 and SERPINA1, AREG, EDA2R, FCRL1, NOTCH1 and TNC, EDA2R, FCRL1, PTX3, SERPINA1 and TNC, FCRL1, NOTCH1, PTX3, SERPINA1 and TNC, A REG, CEACAM5, GDF15, PTX3, and TNC, AREG, COMP, FCRL1, SERPINA1, and TNC, COMP, FCRL1, NOTCH1, SERPINA1, and TMPRSS15, CEACAM5, FCRL1, NOTCH1, PTX3, and SERPINA1, AREG, CEACAM5, GDF15, PTX3, and SERPINA1, AREG, COMP, NOTCH1, PTX3, and SERPINA1, AREG, CEACAM5, FCRL1, GDF15, PTX3, and SERPINA1, AREG, CEACAM 5. FCRL1, NOTCH1 and TNC, AREG, EDA2R, FCRL1, PTX3 and TNC, AREG, COMP, PTX3, SERPINA1 and TNC, CEACAM5, EDA2R, FCRL1, PTX3 and TNC, CEACAM5, FCRL1, NOTCH1, SERPINA1 and TNC, AREG, COMP, NOTCH1, SERPINA1 and TNC, CEACAM5, FCRL1, PTX3, SERPINA1 and TNC, CEACAM5, EDA2R, FCRL1, PTX3 and SERPINA 1, AREG, EDA2R, NOTCH1, SERPINA1, and TNC, AREG, FCRL1, NOTCH1, SERPINA1, and TNC, AREG, CEACAM5, FCRL1, NOTCH1, and SERPINA1, AREG, NOTCH1, PTX3, SERPINA1, and TNC, CEACAM5, FCRL1, GDF15, SERPINA1, and TNC, CEACAM5, EDA2R, FCRL1, GDF15, and TNC, AREG, CEACAM5, FCRL1, PTX3, and TNC, AREG, FCRL1, GDF15, SERPINA1 and TNC, AREG, EDA2R, GDF15, PTX3 and TNC, EDA2R, GDF15, PTX3, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, FCRL1 and GDF15, AREG, GDF15, PTX3, SERPINA1 and TNC, AREG, EDA2R, FCRL1, GDF15 and SERPINA1, AREG, CEACAM5, FCRL1, GDF15 and SERPINA1, AREG, EDA2R, GDF15, PTX3 and SERPINA 1, AREG, CEACAM5, FCRL1, PTX3 and SERPINA1, CEACAM5, EDA2R, PTX3, SERPINA1 and TNC, AREG, EDA2R, FCRL1, GDF15 and TNC, EDA2R, FCRL1, GDF15, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, PTX3 and TNC, CEACAM5, EDA2R, GDF15, SERPINA1 and TNC, CEACAM5, EDA2R, FCRL1, SERPINA1 and TNC, CEACAM5, EDA2 R, FCRL1, GDF15 and SERPINA1, AREG, FCRL1, PTX3, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, PTX3 and SERPINA1, AREG, CEACAM5, EDA2R, GDF15 and TNC, AREG, CEACAM5, EDA2R, FCRL1 and SERPINA1, AREG, CEACAM5, EDA2R, FCRL1 and TNC, AREG, CEACAM5, GDF15, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, GD F15 and SERPINA1, AREG, CEACAM5, PTX3, SERPINA1 and TNC, AREG, EDA2R, FCRL1, SERPINA1 and TNC, AREG, CEACAM5, FCRL1, SERPINA1 and TNC, AREG, CEACAM5, EDA2R, SERPINA1 and TNC, AREG, EDA2R, PTX3, SERPINA1 and TNC, or AREG, EDA2R, GDF15, SERPINA1 and TNC; further COMP, FCRL1, GDF15, NOTCH1 and PTX3.
优选地，所述A包含6markers组合，所述6markers组合为所述B中的任意六种。Preferably, A comprises a combination of 6 markers, and the combination of 6 markers is any six of the combinations in B.
优选地，所述6markers组合为d1)和d2):Preferably, the 6 markers are combined into d1) and d2):
d1)所述5markers组合(优选上述63个5markers组合中的任一种)；d1) the 5-markers combination (preferably any one of the above 63 5-markers combinations);
d2)所述B中的任意一种；d2) any one of B;
所述d2)不同于d1)中所述5markers组合中的任意一个marker。The d2) is different from any one of the markers in the combination of 5 markers in d1).
优选地，所述6markers组合为：SPP1、PLXDC2、SOD3、IL4R、BAG3与PROK1,AREG、CEACAM5、PTX3、CD48、CCL7与IGFBP1,SPP1、PLXDC2、COMP、LMNB2、PROK1与TCL1A,SPP1、LMNB2、FCRL1、SOD3、PLXDC2与BAG3,SPP1、COMP、LMNB2、SOD3、TCL1A与PROK1,SPP1、LMNB2、FCRL1、SOD3、MEGF9与PROK1,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与PROK1,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ADAMTS8,SPP1、COMP、FCRL1、SOD3、LMNB2与TCL1A,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与PLXDC1,SPP1、COMP、LMNB2、FCRL1、PLXDC2与PROK1,AREG、CEACAM5、SOD3、RET、CCL7与MMP12,TMPRSS15、PTX3、COMP、POF1B、PGA4与ITM2A,SPP1、PLXDC2、COMP、IL4R、TCL1A与PROK1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与ADGRE2,PTX3、GDF15、POF1B、THBS4、ADGRE1与EXTL1,NOTCH1、COMP、GDF15、PTX3、PGA4与CEACAM5,PTX3、POF1B、THBS4、ADGRE5、PGA4与NPY,PTX3、LMNB2、SOD3、CNTN4、PGA4与TCL1A,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与ITM2A,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与IL4R,PTX3、COMP、HMCN2、POF1B、PGA4与ADGRE1,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与C9,SPP1、PLXDC2、COMP、LMNB2、TCL1A与CLEC3B,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与CEACAM16,TMPRSS15、PTX3、GDF15、COMP、PGA4与ITM2A,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与TNC,GDF15、SPP1、PLXDC2、COMP、PROK1与LMNB2,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与TNC,PTX3、GDF15、ENPP6、THBS4、ADGRE1与AGR3,AREG、CEACAM5、PTX3、SPP1、PLXDC2与SPON2,AREG、CEACAM5、RET、LPL、KRT19与SPON2,PTX3、GDF15、RET、ADGRG2、BMP4与ADGRE1,TMPRSS15、COMP、PTX3、PGA4、POF1B与NPY,PTX3、POF1B、FCRL1、SOD3、PGA4与ITM2A,PTX3、POF1B、THBS4、FASLG、ITM2A与EXTL1,PTX3、POF1B、THBS4、EXTL1、PGA4与ITM2A,SPP1、COMP、LMNB2、FCRL1、LPL与LBP,PTX3、GDF15、THBS4、EXTL1、ADGRE1与ENPP6,SPP1、COMP、FCRL1、SOD3、CFP与LMNB2,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与IL4R,SPP1、COMP、LMNB2、FCRL1、TNC与CLEC3B,ADGRE1、KRT19、LMNB2、COMP、PTX3与PGA4,PTX3、SPP1、ENPP6、COMP、TCL1A与ADGRE2,PTX3、GDF15、PLXDC2、THBS4、AGR3与TNC,SPP1、ITGA11、FCRL1、SOD3、LMNB2与PLXDC1,SPP1、COMP、LMNB2、FCRL1、PROK1与SOD3,TMPRSS15、PTX3、GDF15、COMP、ADGRE1与PGA4,SPP1、THBS4、LMNB2、ADGRE5、PROK1与BAG3,SPP1、COMP、LMNB2、FCRL1、ADGRE1与PTPRS,PTX3、ITGA11、POF1B、RET、SOD3与PGA4,SPP1、COMP、FCRL1、ADGRE5、LPL与LMNB2,SPP1、COMP、LMNB2、FCRL1、SOD3与CEACAM16,PTX3、GDF15、COMP、ADGRG2、ADGRE1与THBS4,PTX3、COMP、POF1B、FCRL1、PGA4与IL4R,PTX3、GDF15、THBS4、FASLG、TMPRSS15与ITM2A,TMPRSS15、PTX3、POF1B、THBS4、PGA4与CFP,PTX3、GDF15、THBS4、ADGRG2、BMP4与PROK1,PTX3、GDF15、COMP、EXTL1、PGA4与NOTCH1,ADGRE1、LMNB2、THBS4、TMPRSS15、GDF15与TNC,SPP1、COMP、LMNB2、SOD3、FCRL1与ASAH2,SPP1、COMP、FCRL1、ADGRE5、LMNB2与TNC,SPP1、PLXDC2、COMP、LMNB2、FCRL1与PLXDC1,SPP1、ADGRG2、FCRL1、SOD3、BAG3与LMNB2,GSN、TMPRSS15、PGA4、PTX3、POF1B与SOD3,TMPRSS15、PTX3、THBS4、FASLG、MMP12与ITM2A,TMPRSS15、PTX3、GDF15、THBS4、CCL7与ADGRE1,COMP、FCRL1、PTX3、GDF15、NOTCH1与PGA4,SPP1、THBS4、LMNB2、ADGRE5、CLEC3B与PROK1,PTX3、GDF15、THBS4、ADGRG2、PROK1与TCL1A,SPP1、COMP、LMNB2、FCRL1、CLEC3B与BAG3,TMPRSS15、SPP1、FCRL1、SOD3、PLXDC1与EDA2R,PTX3、GDF15、POF1B、THBS4、ADGRE5与TNC,TMPRSS15、PTX3、THBS4、FASLG、GDF15与AREG,SPP1、COMP、FCRL1、SOD3、TCL1A与LPL,PTX3、GDF15、THBS4、FASLG、ADGRE1与POF1B,TMPRSS15、PTX3、GDF15、THBS4、FASLG与TNC,PTX3、GDF15、THBS4、EXTL1、ITM2A与TNC,SPP1、LMNB2、FCRL1、SOD3、COMP与TMPRSS15,SPP1、LMNB2、SOD3、ADGRE5、FCRL1与NT5C1A,PTX3、GDF15、COMP、THBS4、ADGRE1与ITGA2,SPP1、PLXDC2、FCRL1、SOD3、ESM1与BAG3,TMPRSS15、PTX3、SPP1、THBS4、AREG与FASLG,SPP1、COMP、LMNB2、FASLG、FCRL1与TCL1A，SPP1、PLXDC2、COMP、LMNB2、PROK1与BAG3,AREG、CEACAM5、PTX3、CD48、CCL7与IGSF3,SPP1、PLXDC2、COMP、LMNB2、PROK1与DCC,SPP1、COMP、FCRL1、SOD3、LMNB2与ADGRE1,AREG、CEACAM5、PTX3、CD48、CCL7与NOTCH3,SPP1、LMNB2、FCRL1、SOD3、MEGF9与CDH23,SPP1、COMP、LMNB2、FCRL1、PLXDC2与ESM1,AREG、CEACAM5、PTX3、CD48、CCL7与PLXDC2,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与EXTL1,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与EDA2R,SPP1、PLXDC2、COMP、LMNB2、PROK1与FCER2,AREG、CEACAM5、SOD3、RET、CCL7与ENPP6,SPP1、LMNB2、FCRL1、SOD3、AGR3与PLXDC1,SPP1、COMP、LMNB2、SOD3、TCL1A与PLXDC2,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与TCL1A,SPP1、PLXDC2、COMP、LMNB2、PROK1与THBS4,SPP1、PLXDC2、COMP、LMNB2、PROK1与CCL7,SPP1、COMP、FCRL1、SOD3、LMNB2与GCG,AREG、CEACAM5、SOD3、RET、CCL7与EXTL1,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与ADGRG2,SPP1、LMNB2、FCRL1、SOD3、MEGF9与PLXDC1,SPP1、COMP、LMNB2、SOD3、TCL1A与ITM2A,PTX3、GDF15、POF1B、THBS4、ADGRE1与PKD1,AREG、CEACAM5、SOD3、RET、CCL7与ADAMTS8,TMPRSS15、PTX3、COMP、POF1B、PGA4与ESM1,PTX3、LMNB2、SOD3、CNTN4、PGA4与ADGRE1,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与SPON2,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ADGRE5,PTX3、GDF15、POF1B、THBS4、ADGRE1与CDH23,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与TMPRSS15,PTX3、COMP、HMCN2、POF1B、PGA4与PLXDC1,AREG、CEACAM5、SOD3、RET、CCL7与GNAS,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与CLEC3B,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与ADGRE1,SPP1、COMP、LMNB2、SOD3、TCL1A与SELL,SPP1、PLXDC2、COMP、LMNB2、PROK1与PLXDC1,AREG、CEACAM5、PTX3、CD48、CCL7与POF1B,SPP1、COMP、LMNB2、FCRL1、PLXDC2与TCL1A,AREG、CEACAM5、SOD3、RET、CCL7与POF1B,PTX3、GDF15、POF1B、THBS4、ADGRE1与TNC,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与IL6,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与TCL1A,AREG、CEACAM5、PTX3、CD48、CCL7与ITGAM,SPP1、PLXDC2、COMP、LMNB2、PROK1与SOD3,SPP1、PLXDC2、COMP、LMNB2、PROK1与IL4R,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与GNAS,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与PTPRS,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与PLXDC1,SPP1、COMP、FCRL1、SOD3、LMNB2与TNC,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ITGA2,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与SPP1,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与CNTN4,SPP1、COMP、FCRL1、SOD3、LMNB2与C9,NOTCH1、COMP、GDF15、PTX3、PGA4与ADGRE1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与CNTN4,SPP1、COMP、FCRL1、CLEC3B、LMNB2与TCL1A,AREG、CEACAM5、PTX3、CD48、CCL7与ASAH2,AREG、CEACAM5、SOD3、RET、CCL7与ITGAM,AREG、CEACAM5、SOD3、RET、CCL7与ITM2A,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与ITGA11,AREG、CEACAM5、RET、LPL、KRT19与PTPRS,AREG、CEACAM5、SOD3、RET、CCL7与IGSF3,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与PLXDC2,SPP1、PLXDC2、COMP、LMNB2、PROK1与MEGF9,PTX3、POF1B、FCRL1、SOD3、PGA4与PLXDC1,AREG、CEACAM5、PTX3、SPP1、PLXDC2与TMPRSS15,AREG、CEACAM5、SOD3、RET、CCL7与CFP,PTX3、POF1B、THBS4、EXTL1、PGA4与ADGRE1,SPP1、LMNB2、FCRL1、SOD3、ITGB1与PLXDC1,PTX3、POF1B、THBS4、ADGRE5、PGA4与ITM2A,SPP1、COMP、LMNB2、SOD3、ADGRE1与PROK1,TMPRSS15、PTX3、COMP、POF1B、PGA4与CKAP4,TMPRSS15、PTX3、COMP、POF1B、PGA4与ADGRE1,TMPRSS15、PTX3、COMP、POF1B、PGA4与THBS4,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与BAG3,TMPRSS15、PTX3、COMP、POF1B、PGA4与NPY,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与PROK1,PTX3、GDF15、POF1B、THBS4、ADGRE1与AREG,SPP1、COMP、LMNB2、SOD3、TCL1A与CEACAM16,SPP1、PLXDC2、COMP、LMNB2、PROK1与MMP12,AREG、CEACAM5、SOD3、RET、CCL7与DLK1,SPP1、COMP、LMNB2、SOD3、TCL1A与CNTN4,AREG、CEACAM5、PTX3、CD48、CCL7与CDH23,SPP1、PLXDC2、COMP、LMNB2、PROK1与ADGRE5,NOTCH1、COMP、GDF15、PTX3、PGA4与ITM2A,PTX3、POF1B、THBS4、EXTL1、PGA4与SOD3,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与ITGA11,SPP1、COMP、FCRL1、SOD3、LMNB2与NOS2,PTX3、GDF15、POF1B、THBS4、ADGRE1与LMNB2,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与THBS4,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与AGR3,SPP1、PLXDC2、COMP、LMNB2、PROK1与LPL,GDF15、SPP1、PLXDC2、COMP、PROK1与ADAMTS8,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与CEACAM16,PTX3、GDF15、POF1B、THBS4、ADGRE1与CFP,SPP1、COMP、LMNB2、SOD3、TCL1A与MEGF9,SPP1、PLXDC2、COMP、LMNB2、PROK1与GNAS,SPP1、PLXDC2、COMP、LMNB2、PROK1与AGR3,AREG、CEACAM5、SOD3、RET、CCL7与PTPRS,TMPRSS15、PTX3、COMP、POF1B、PGA4与IL4R,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ESM1,SPP1、LMNB2、FCRL1、SOD3、AGR3与PLXDC2,TMPRSS15、PTX3、COMP、POF1B、PGA4与IGFBP1,AREG、CEACAM5、RET、LPL、KRT19与IL4R,AREG、CEACAM5、SOD3、RET、CCL7与IL4R,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与GCG,SPP1、COMP、FCRL1、SOD3、LMNB2与PLXDC1,SPP1、COMP、LMNB2、FCRL1、PLXDC2与TNC,PTX3、POF1B、THBS4、EXTL1、PGA4与CLEC3B,SPP1、COMP、LMNB2、SOD3、ADGRE1与TCL1A,TMPRSS15、PTX3、COMP、POF1B、PGA4与GDF15,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与BMP4,PTX3、GDF15、THBS4、ADGRE5、ADGRE1与TNC,PTX3、POF1B、THBS4、EXTL1、PGA4与PCDH7,AREG、CEACAM5、PTX3、SPP1、PLXDC2与FAP,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与BMP4,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与AREG,PTX3、GDF15、THBS4、EXTL1、ADGRE1与TNC,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与BAG3,AREG、CEACAM5、SOD3、RET、CCL7与SPP1,SPP1、COMP、FCRL1、SOD3、LMNB2与PLXDC2,SPP1、COMP、LMNB2、SOD3、TCL1A与CLEC3B,SPP1、COMP、LMNB2、SOD3、ADGRE1与LPL,AREG、CEACAM5、PTX3、CD48、CCL7与CLEC3B,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与CDH23,SPP1、PLXDC2、COMP、LMNB2、TCL1A与IGFBP1,PTX3、GDF15、RET、ADGRG2、BMP4与FASLG,AREG、CEACAM5、PTX3、CD48、CCL7与ENPP6,AREG、CEACAM5、PTX3、CD48、CCL7与ITGB1,SPP1、COMP、LMNB2、SOD3、ADGRE1与CFP,SPP1、PLXDC2、COMP、LMNB2、TCL1A与ADGRE5,PTX3、POF1B、FCRL1、SOD3、PGA4与TMPRSS15,NOTCH1、COMP、GDF15、PTX3、PGA4与FCER2,PTX3、COMP、HMCN2、POF1B、PGA4与ITM2A,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与GNAS,PTX3、LMNB2、SOD3、CNTN4、PGA4与RET,SPP1、COMP、LMNB2、FCRL1、LPL与PLXDC2,SPP1、PLXDC2、COMP、LMNB2、TCL1A与POF1B,AREG、CEACAM5、PTX3、SPP1、PLXDC2与DCC,SPP1、COMP、FCRL1、SOD3、LMNB2与FCER2,SPP1、COMP、FCRL1、SOD3、LMNB2与SERPINA1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与FCRL1,NOTCH1、COMP、GDF15、PTX3、PGA4与DLK1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与ITGB1,AREG、CEACAM5、SOD3、RET、CCL7与THBS4,PTX3、POF1B、THBS4、ADGRE5、PGA4与ENPP6,AREG、CEACAM5、PTX3、CD48、CCL7与DLK1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与COMP,SPP1、PLXDC2、COMP、LMNB2、PROK1与POF1B,PTX3、GDF15、ENPP6、THBS4、ADGRE1与BMP4,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与TCL1A,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与AREG,PTX3、GDF15、POF1B、THBS4、ADGRE1与PTPRS,SPP1、COMP、LMNB2、FCRL1、SOD3与CDH23,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与LMNB2,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ANGPTL4,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ENPP6,AREG、CEACAM5、PTX3、SPP1、PLXDC2与CNTN4,SPP1、PLXDC2、COMP、LMNB2、PROK1与PGA4,AREG、CEACAM5、SOD3、RET、CCL7与ITGB1,SPP1、COMP、LMNB2、FCRL1、LPL与TCL1A,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与CLEC3B,SPP1、PLXDC2、COMP、IL4R、TCL1A与DCC,AREG、CEACAM5、SOD3、RET、CCL7与ESM1,PTX3、GDF15、COMP、ADGRG2、ADGRE1与PGA4,SPP1、PLXDC2、COMP、LMNB2、PROK1与NOS2,AREG、CEACAM5、SOD3、RET、CCL7与C9,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与PGA4,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与FCRL1,AREG、CEACAM5、SOD3、RET、CCL7与EDA2R,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与BAG3,NOTCH1、COMP、GDF15、PTX3、PGA4与ADGRE2,AREG、CEACAM5、SOD3、RET、CCL7与GCG,SPP1、COMP、LMNB2、SOD3、TCL1A与PLXDC1,SPP1、COMP、LMNB2、SOD3、TCL1A与ITGB1,PTX3、POF1B、THBS4、FASLG、ITM2A与PCDH7,TMPRSS15、COMP、PTX3、PGA4、POF1B与FASLG,AREG、CEACAM5、SOD3、RET、CCL7与SPON2,SPP1、COMP、LMNB2、FCRL1、LPL与IFNL1,AREG、CEACAM5、PTX3、SPP1、PLXDC2与ITGA2,AREG、CEACAM5、SOD3、RET、CCL7与FAP,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与RET,SPP1、PLXDC2、COMP、LMNB2、PROK1与TNC,SPP1、LMNB2、FCRL1、SOD3、MEGF9与LPL,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与GRK5,AREG、CEACAM5、SOD3、RET、CCL7与CDH23,SPP1、COMP、LMNB2、FCRL1、LPL与GSN,SPP1、PLXDC2、COMP、LMNB2、PROK1与SERPINA1,TMPRSS15、COMP、PTX3、PGA4、POF1B与FCRL1,PTX3、POF1B、THBS4、EXTL1、PGA4与PROK1,AREG、CEACAM5、PTX3、CD48、CCL7与ADGRE1,AREG、CEACAM5、SOD3、RET、CCL7与IFNL1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与ADGRE1,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与CDH23,SPP1、COMP、LMNB2、SOD3、TCL1A与ADGRE5,SPP1、COMP、LMNB2、FCRL1、SOD3与MEGF9,AREG、CEACAM5、PTX3、SPP1、PLXDC2与C9,PTX3、GDF15、POF1B、THBS4、ADGRE1与NPY,SPP1、PLXDC2、COMP、LMNB2、PROK1与IGDCC4,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与PROK1,TMPRSS15、PTX3、GDF15、COMP、PGA4与ENPP6,SPP1、COMP、LMNB2、FCRL1、LPL与CLEC3B,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与NOTCH3,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与CEACAM16,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与BMP4,TMPRSS15、PTX3、GDF15、THBS4、PGA4与ITM2A,TMPRSS15、PTX3、GDF15、COMP、PGA4与C9,TMPRSS15、COMP、PTX3、PGA4、POF1B与TNC,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与TNFRSF10B,PTX3、GDF15、POF1B、THBS4、ADGRE1与ITGA11,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与TNC,AREG、CEACAM5、SOD3、RET、CCL7与ADGRE5,PTX3、GDF15、POF1B、THBS4、ADGRE1与LPL,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与THBS4,PTX3、GDF15、POF1B、THBS4、ADGRE1与ITM2A,PTX3、GDF15、THBS4、EXTL1、ADGRE1与ITM2A,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与PROK1,PTX3、LMNB2、SOD3、CNTN4、PGA4与MEGF9,SPP1、LMNB2、FCRL1、SOD3、MEGF9与PGA4,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与TCL1A,SPP1、COMP、LMNB2、FCRL1、ADGRE1与TCL1A,PTX3、COMP、POF1B、FCRL1、PGA4与TMPRSS15,NOTCH1、COMP、GDF15、PTX3、PGA4与AGR3,PTX3、GDF15、ENPP6、THBS4、ADGRE1与AREG,SPP1、PLXDC2、COMP、LMNB2、PROK1与PCDH7,PTX3、GDF15、POF1B、THBS4、ADGRE1与ITGA2,SPP1、COMP、LMNB2、SOD3、TCL1A与FCER2,SPP1、PLXDC2、COMP、LMNB2、PROK1与IL6,SPP1、THBS4、LMNB2、ADGRE5、PROK1与PLXDC2,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与IL4R,SPP1、PLXDC2、COMP、LMNB2、PROK1与PTPRS,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与DLK1,PTX3、GDF15、ENPP6、THBS4、ADGRE1与ITGA11,AREG、CEACAM5、PTX3、CD48、CCL7与ADAMTS8,AREG、CEACAM5、SOD3、RET、CCL7与BAG3,SPP1、COMP、FCRL1、SOD3、LMNB2与ITGA2,PTX3、GDF15、COMP、ADGRG2、ADGRE1与TCL1A,PTX3、POF1B、THBS4、ADGRE5、PGA4与GSN,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与DCC,AREG、CEACAM5、PTX3、CD48、CCL7与AGR3,AREG、CEACAM5、PTX3、CD48、CCL7与GDF15,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与ADGRE5,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与TCL1A,SPP1、PLXDC2、COMP、LMNB2、PROK1与ITGA2,TMPRSS15、COMP、PTX3、PGA4、POF1B与ITM2A,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与MEGF9,PTX3、GDF15、POF1B、THBS4、ADGRE1与GSN,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与BAG3,AREG、CEACAM5、SOD3、RET、CCL7与SERPINA1,PTX3、GDF15、POF1B、THBS4、ADGRE1与ADGRE5,SPP1、COMP、FCRL1、SOD3、LMNB2与LPL,SPP1、COMP、FCRL1、CLEC3B、LMNB2与ADGRE1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与CFP,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与ITM2A,TMPRSS15、PTX3、POF1B、THBS4、PGA4与SOD3,NOTCH1、COMP、GDF15、PTX3、PGA4与ADAMTS8,AREG、CEACAM5、RET、LPL、KRT19与C9,AREG、CEACAM5、RET、LPL、KRT19与ESM1,AREG、CEACAM5、SOD3、RET、CCL7与TNFRSF10B,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与TCL1A,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与GCG,SPP1、COMP、FCRL1、SOD3、LMNB2与ITIH3,PTX3、GDF15、POF1B、THBS4、ADGRE1与BMP4,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与IFNL1,AREG、CEACAM5、SOD3、RET、CCL7与IGFBP1,SPP1、COMP、LMNB2、SOD3、FCRL1与ITM2A,TMPRSS15、PTX3、GDF15、COMP、PGA4与BMP4,SPP1、PLXDC2、COMP、LMNB2、PROK1与ADAMTS8,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与RET,TMPRSS15、PTX3、GDF15、THBS4、PGA4与CLEC3B,ADGRE1、LMNB2、THBS4、TMPRSS15、GDF15与CLEC3B,SPP1、COMP、FCRL1、CLEC3B、LMNB2与FCER2,SPP1、PLXDC2、COMP、LMNB2、PROK1与TNFRSF10B,AREG、CEACAM5、PTX3、CD48、CCL7与IFNL1,SPP1、PLXDC2、COMP、IL4R、TCL1A与LMNB2,PTX3、GDF15、THBS4、EXTL1、ADGRE1与AGR3,SPP1、COMP、LMNB2、SOD3、TCL1A与AREG,AREG、CEACAM5、PTX3、CD48、CCL7与MMP12,AREG、CEACAM5、SOD3、RET、CCL7与DCC,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与POF1B,SPP1、COMP、LMNB2、SOD3、TCL1A与ASAH2,SPP1、COMP、LMNB2、FCRL1、LPL与PROK1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与DLK1,SPP1、PLXDC2、COMP、LMNB2、PROK1与FGF21,SPP1、PLXDC2、SOD3、IL4R、BAG3与LMNB2,SPP1、COMP、FCRL1、SOD3、LMNB2与GRK5,AREG、CEACAM5、RET、LPL、KRT19与TMPRSS15,SPP1、COMP、FCRL1、CLEC3B、LMNB2与SOD3,PTX3、GDF15、ENPP6、THBS4、ADGRE1与TNC,AREG、CEACAM5、PTX3、CD48、CCL7与FAP,PTX3、COMP、POF1B、FCRL1、PGA4与CLEC3B,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与IFNL1,SPP1、COMP、LMNB2、FCRL1、PLXDC2与CLEC3B,NOTCH1、COMP、GDF15、PTX3、PGA4与TCL1A,TMPRSS15、PTX3、GDF15、COMP、PGA4与FCRL1,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与ADGRG2,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与AREG,SPP1、LMNB2、FCRL1、SOD3、TCL1A与PROK1,PTX3、GDF15、COMP、ADGRG2、ADGRE1与DCC,PTX3、GDF15、THBS4、EXTL1、ADGRE1与BMP4,SPP1、PLXDC2、COMP、LMNB2、PROK1与PKD1,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与FAP,AREG、CEACAM5、PTX3、CD48、CCL7与PTPRS,PTX3、GDF15、COMP、ADGRG2、ADGRE1与RET,SPP1、COMP、LMNB2、FCRL1、LPL与PTPRS,TMPRSS15、PTX3、COMP、POF1B、PGA4与FASLG,SPP1、THBS4、LMNB2、ADGRE5、PROK1与SOD3,GSN、TMPRSS15、PGA4、PTX3、POF1B与COMP,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与PGA4,TMPRSS15、PTX3、COMP、POF1B、PGA4与IFNL1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与NT5C1A,SPP1、PLXDC2、COMP、LMNB2、TCL1A与CNTN1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与ADGRE5,PTX3、LMNB2、SOD3、CNTN4、PGA4与ITM2A,PTX3、COMP、HMCN2、POF1B、PGA4与NOTCH1,SPP1、LMNB2、FCRL1、SOD3、ITGB1与COMP,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与AGR3,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与SOD3,AREG、CEACAM5、RET、LPL、KRT19与PLXDC2,NOTCH1、COMP、GDF15、PTX3、PGA4与PCDH7,GDF15、SPP1、PLXDC2、COMP、PROK1与FCER2,AREG、CEACAM5、PTX3、SPP1、PLXDC2与ADGRE5,PTX3、POF1B、FCRL1、SOD3、PGA4与EXTL1,SPP1、COMP、FCRL1、CLEC3B、LMNB2与PROK1,PTX3、POF1B、THBS4、EXTL1、PGA4与BAG3,SPP1、COMP、LMNB2、FCRL1、ADGRE1与LPL,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与NOTCH1,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与ITIH3,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与GDF15,PTX3、COMP、POF1B、FCRL1、PGA4与ITM2A,TMPRSS15、PTX3、COMP、POF1B、PGA4与NT5C1A,SPP1、PLXDC2、COMP、LMNB2、TCL1A与TNC,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与PTX3,TMPRSS15、PTX3、GDF15、THBS4、PGA4与COMP,SPP1、PLXDC2、COMP、LMNB2、TCL1A与VSIG4,SPP1、COMP、LMNB2、SOD3、TCL1A与TNC,PTX3、COMP、POF1B、FCRL1、PGA4与PLXDC1,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与ADGRE1,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与AREG,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与FASLG,NOTCH1、COMP、GDF15、PTX3、PGA4与PKD1,PTX3、GDF15、POF1B、THBS4、ADGRE1与CEACAM16,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与GNAS,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与TCL1A,SPP1、PLXDC2、COMP、LMNB2、PROK1与ASAH2,SPP1、PLXDC2、COMP、IL4R、TCL1A与DLK1,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与PGA4,SPP1、COMP、FCRL1、ADGRE5、LMNB2与PROK1,AREG、CEACAM5、RET、LPL、KRT19与ENPP6,PTX3、LMNB2、SOD3、CNTN4、PGA4与BMP4,SPP1、PLXDC2、COMP、LMNB2、PROK1与IGSF3,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与PLXDC1,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与CLEC3B,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与CLEC3B,SPP1、LMNB2、FCRL1、SOD3、MEGF9与ITGA11,SPP1、PLXDC2、COMP、LMNB2、PROK1与ITGB1,AREG、CEACAM5、SOD3、RET、CCL7与NTRK2,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与PROK1,SPP1、COMP、FCRL1、CLEC3B、LMNB2与PGA4,SPP1、COMP、LMNB2、FCRL1、SOD3与AREG,PTX3、COMP、HMCN2、POF1B、PGA4与FASLG,PTX3、LMNB2、SOD3、CNTN4、PGA4与TNC,SPP1、COMP、LMNB2、FCRL1、PLXDC2与NOS2,SPP1、PLXDC2、COMP、LMNB2、TCL1A与ADGRG2,SPP1、PLXDC2、COMP、LMNB2、PROK1与NT5C1A,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与FAP,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与RBFOX3,SPP1、COMP、LMNB2、SOD3、FCRL1与VSIG4,PTX3、COMP、HMCN2、POF1B、PGA4与LMNB2,PTX3、POF1B、FCRL1、SOD3、PGA4与ADGRE5,AREG、CEACAM5、PTX3、CD48、CCL7与TMPRSS15,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与CNTN4,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与FASLG,SPP1、COMP、LMNB2、SOD3、FCRL1与ADGRG2,SPP1、ITGA11、FCRL1、SOD3、LMNB2与PLXDC2,SPP1、PLXDC2、COMP、LMNB2、PROK1与BMP4,TMPRSS15、PTX3、COMP、POF1B、PGA4与CCL7,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与GRK5,SPP1、COMP、FCRL1、CLEC3B、LMNB2与NOS2,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与GRK5,AREG、CEACAM5、SOD3、RET、CCL7与TMPRSS15,SPP1、COMP、LMNB2、FCRL1、PROK1与ADGRG2,SPP1、COMP、FCRL1、SOD3、LMNB2与CCL7,AREG、CEACAM5、SOD3、RET、CCL7与ITGA11,TMPRSS15、PTX3、POF1B、THBS4、PGA4与ITM2A,TMPRSS15、PTX3、COMP、POF1B、PGA4与TNFRSF10B,AREG、CEACAM5、RET、LPL、KRT19与ADGRE1,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与BAG3,SPP1、ITGA11、FCRL1、SOD3、LMNB2与TCL1A,TMPRSS15、PTX3、GDF15、THBS4、FGF21与ADGRE1,SPP1、COMP、LMNB2、SOD3、TCL1A与GRK5,PTX3、POF1B、THBS4、EXTL1、PGA4与PTPRS,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与PGA4,SPP1、COMP、FCRL1、CLEC3B、LMNB2与CEACAM16,SPP1、COMP、FCRL1、CLEC3B、LMNB2与AGR3,PTX3、GDF15、POF1B、THBS4、ADGRE1与IL6,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与TNC,SPP1、COMP、FCRL1、ADGRE5、LMNB2与PLXDC1,PTX3、POF1B、FCRL1、SOD3、PGA4与NPY,PTX3、POF1B、THBS4、EXTL1、PGA4与LPL,SPP1、COMP、FCRL1、SOD3、LMNB2与BAG3,TMPRSS15、SPP1、FCRL1、SOD3、PLXDC1与CKAP4,TMPRSS15、PTX3、POF1B、THBS4、PGA4与ITGA11,TMPRSS15、PTX3、GDF15、COMP、PGA4与MMP12,NOTCH1、COMP、GDF15、PTX3、PGA4与BMP4,SPP1、COMP、LMNB2、SOD3、TCL1A与DLK1,NOTCH1、COMP、GDF15、PTX3、PGA4与PLXDC1,SPP1、COMP、LMNB2、FCRL1、SOD3与PKD1,SPP1、COMP、FCRL1、SOD3、LMNB2与PGA4,TMPRSS15、PTX3、COMP、POF1B、PGA4与CDH23,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与ITM2A,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与CFP,AREG、CEACAM5、PTX3、CD48、CCL7与ITGA2,AREG、CEACAM5、RET、LPL、KRT19与PLXDC1,PTX3、COMP、HMCN2、POF1B、PGA4与LPL,SPP1、COMP、FCRL1、SOD3、LMNB2与IFNL1,SPP1、PLXDC2、COMP、LMNB2、TCL1A与IL6,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与IL4R,TMPRSS15、COMP、PTX3、PGA4、POF1B与GDF15,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与LPL,TMPRSS15、COMP、PTX3、PGA4、POF1B与LMNB2,SPP1、THBS4、LMNB2、ADGRE5、CLEC3B与FCRL1,TMPRSS15、PTX3、COMP、POF1B、PGA4与PROK1,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与ADGRE2,NOTCH1、COMP、GDF15、PTX3、PGA4与EXTL1,SPP1、COMP、LMNB2、FCRL1、SOD3与AGR3,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与DCC,GDF15、SPP1、PLXDC2、COMP、PROK1与BAG3,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与C9,AREG、CEACAM5、SOD3、RET、CCL7与PLXDC2,PTX3、GDF15、COMP、ADGRG2、ADGRE1与ADGRE2,SPP1、PLXDC2、COMP、LMNB2、PROK1与CLEC3B,TMPRSS15、SPP1、FCRL1、SOD3、PLXDC1与PGA4,AREG、CEACAM5、PTX3、CD48、CCL7与TNFRSF10B,AREG、CEACAM5、SOD3、RET、CCL7与NOTCH3,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与POF1B,SPP1、PLXDC2、COMP、LMNB2、TCL1A与ITGA11,PTX3、SPP1、ENPP6、COMP、TCL1A与ADGRE5,PTX3、POF1B、FCRL1、SOD3、PGA4与ADGRE2,PTX3、ITGA11、POF1B、RET、SOD3与TNC,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与LMNB2,SPP1、PLXDC2、SOD3、IL4R、BAG3与CEACAM16,SPP1、COMP、LMNB2、FCRL1、ADGRE1与MMP12,NOTCH1、COMP、GDF15、PTX3、PGA4与POF1B,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与SELL,TMPRSS15、COMP、PTX3、PGA4、POF1B与CLEC3B,TMPRSS15、PTX3、COMP、POF1B、PGA4与SOD3,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与FASLG,PTX3、GDF15、POF1B、THBS4、ADGRE1与SPON2,PTX3、ITGA11、POF1B、RET、SOD3与LMNB2,SPP1、LMNB2、FCRL1、SOD3、TCL1A与ITGA2,SPP1、PLXDC2、COMP、LMNB2、TCL1A与FASLG,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与IL6,PTX3、POF1B、THBS4、EXTL1、PGA4与IFNL1,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与ITIH3,PTX3、GDF15、THBS4、ADGRG2、PROK1与ADGRE2,AREG、CEACAM5、SOD3、RET、CCL7与ANGPTL4,PTX3、COMP、HMCN2、POF1B、PGA4与NPY,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与COMP,SPP1、PLXDC2、COMP、LMNB2、PROK1与ESM1,TMPRSS15、COMP、PTX3、PGA4、POF1B与PCDH7,SPP1、LMNB2、FCRL1、SOD3、TCL1A与CNTN4,SPP1、COMP、FCRL1、ADGRE5、LMNB2与SOD3,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与ITGA2,ADGRE1、LMNB2、THBS4、TMPRSS15、GDF15与CFP,PTX3、GDF15、PLXDC2、THBS4、AGR3与ITM2A,SPP1、COMP、FCRL1、SOD3、LMNB2与NPY,PTX3、COMP、POF1B、FCRL1、PGA4与PCDH7,PTX3、POF1B、FCRL1、SOD3、PGA4与PCDH7,SPP1、PLXDC2、COMP、LMNB2、TCL1A与GDF15,TMPRSS15、PTX3、GDF15、COMP、PGA4与PKD1,SPP1、PLXDC2、COMP、IL4R、TCL1A与CKAP4,TMPRSS15、PTX3、COMP、POF1B、PGA4与FGF21,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与GSN,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与TNC,SPP1、PLXDC2、COMP、LMNB2、TCL1A与LPL,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与PLXDC2,SPP1、PLXDC2、COMP、IL4R、TCL1A与PGA4,SPP1、COMP、LMNB2、FCRL1、SOD3与GNAS,PTX3、GDF15、ENPP6、THBS4、ADGRE1与POF1B,SPP1、PLXDC2、COMP、IL4R、TCL1A与THBS4,TMPRSS15、PTX3、COMP、POF1B、PGA4与MMP12,TMPRSS15、PTX3、GDF15、COMP、PGA4与GNAS,SPP1、COMP、LMNB2、SOD3、TCL1A与PTX3,TMPRSS15、PTX3、COMP、POF1B、PGA4与CFP,AREG、CEACAM5、RET、LPL、KRT19与ITGA2,SPP1、COMP、LMNB2、SOD3、TCL1A与C9,PTX3、POF1B、THBS4、EXTL1、PGA4与GSN,AREG、CEACAM5、PTX3、CD48、CCL7与CNTN4,SPP1、COMP、FCRL1、SOD3、LMNB2与ENPP6,NOTCH1、COMP、GDF15、PTX3、PGA4与FCRL1,SPP1、COMP、LMNB2、FCRL1、PLXDC2与SERPINA1,AREG、CEACAM5、PTX3、CD48、CCL7与C9,AREG、CEACAM5、PTX3、CD48、CCL7与PLXDC1,AREG、CEACAM5、SOD3、RET、CCL7与PTX3,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与NOS2,SPP1、PLXDC2、COMP、LMNB2、FCRL1与ADGRE1,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与TNC,PTX3、POF1B、THBS4、EXTL1、PGA4与TMPRSS15,AREG、CEACAM5、RET、LPL、KRT19与IFNL1,TMPRSS15、COMP、PTX3、PGA4、POF1B与DLK1,SPP1、COMP、LMNB2、SOD3、ADGRE1与PLXDC1,PTX3、COMP、POF1B、FCRL1、PGA4与MEGF9,SPP1、PLXDC2、COMP、LMNB2、TCL1A与BAG3,SPP1、COMP、FCRL1、ADGRE5、LMNB2与PLXDC2,SPP1、COMP、LMNB2、FCRL1、PLXDC2与IL4R,SPP1、COMP、FCRL1、SOD3、LMNB2与ESM1,PTX3、GDF15、THBS4、ADGRE5、ADGRE1与CFP,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与ITGA11,TMPRSS15、PTX3、COMP、POF1B、PGA4与GRK5,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与CLEC3B,SPP1、LMNB2、FCRL1、SOD3、COMP与EXTL1,SPP1、COMP、FCRL1、CLEC3B、LMNB2与CFP,SPP1、LMNB2、FCRL1、SOD3、TCL1A与THBS4,SPP1、COMP、LMNB2、FCRL1、SOD3与PCDH7,SPP1、COMP、FCRL1、CLEC3B、LMNB2与IFNL1,SPP1、LMNB2、SOD3、ADGRE5、FCRL1与NOS2,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与ENPP6,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ITGA11,AREG、CEACAM5、RET、LPL、KRT19与EXTL1,SPP1、LMNB2、SOD3、ADGRE5、PLXDC1与ITM2A,PTX3、POF1B、THBS4、ADGRE5、PGA4与TNC,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与ADAMTS8,TMPRSS15、PTX3、COMP、POF1B、PGA4与ENPP6,SPP1、COMP、LMNB2、SOD3、FCRL1与DLK1,SPP1、PLXDC2、COMP、LMNB2、PROK1与ENPP6,TMPRSS15、COMP、PTX3、PGA4、POF1B与PROK1,PTX3、GDF15、POF1B、THBS4、ADGRE1与IL4R,TMPRSS15、PTX3、GDF15、THBS4、FASLG与GNAS,SPP1、PLXDC2、COMP、LMNB2、PROK1与CNTN5,AREG、CEACAM5、RET、LPL、KRT19与COMP,NOTCH1、COMP、GDF15、PTX3、PGA4与ASAH2,PTX3、GDF15、RET、ADGRG2、BMP4与AGR3,TMPRSS15、PTX3、POF1B、THBS4、PGA4与ADGRE1,TMPRSS15、PTX3、COMP、POF1B、PGA4与ASAH2,SPP1、LMNB2、FCRL1、SOD3、PLXDC2与ESM1,TMPRSS15、PTX3、GDF15、COMP、PGA4与FGF21,PTX3、GDF15、RET、ADGRG2、BMP4与PROK1,SPP1、PLXDC2、SOD3、IL4R、BAG3与ESM1,SPP1、COMP、LMNB2、SOD3、TCL1A与ADGRG2,TMPRSS15、PTX3、POF1B、THBS4、PGA4与BMP4,SPP1、COMP、LMNB2、FCRL1、LPL与GNAS,AREG、CEACAM5、PTX3、CD48、CCL7与FCRL1,AREG、CEACAM5、SOD3、RET、CCL7与ITGA2,SPP1、LMNB2、SOD3、ADGRE5、FCRL1与ITM2A,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与TMPRSS15,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与LBP,SPP1、COMP、FCRL1、CLEC3B、LMNB2与ITIH3,SPP1、COMP、LMNB2、FCRL1、PLXDC2与GCG,SPP1、LMNB2、FCRL1、SOD3、PLXDC2与GCG,AREG、CEACAM5、SOD3、RET、CCL7与GRK5,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与CD48,TMPRSS15、COMP、PTX3、PGA4、POF1B与CNTN5,SPP1、LMNB2、FCRL1、SOD3、TCL1A与ITM2A,PTX3、GDF15、POF1B、THBS4、ADGRE1与BAG3,PTX3、POF1B、THBS4、FASLG、ITM2A与ADGRG2,PTX3、LMNB2、SOD3、CNTN4、PGA4与ESM1,SPP1、COMP、LMNB2、FCRL1、LPL与ITM2A,AREG、CEACAM5、PTX3、CD48、CCL7与BMP4,AREG、CEACAM5、PTX3、CD48、CCL7与EDA2R,PTX3、COMP、HMCN2、POF1B、PGA4与CNTN4,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与FASLG,TMPRSS15、COMP、PTX3、PGA4、POF1B与AREG,PTX3、LMNB2、SOD3、CNTN4、PGA4与GRK5,SPP1、THBS4、LMNB2、ADGRE5、PROK1与ENPP6,或PTX3、GDF15、THBS4、ADGRG2、PROK1与BMP4。Preferably, the 6 markers combination is: SPP1, PLXDC2, SOD3, IL4R, BAG3 and PROK1, AREG, CEACAM5, PTX3, CD48, CCL7 and IGFBP1, SPP1, PLXDC2, COMP, LMNB2, PROK1 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, PLXDC2 and BAG3, SPP1, COMP, LMNB2, SOD3, TCL1A and PROK1, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and PROK1, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and PROK1, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ADAMTS8, SPP1, COMP, FCRL1, SOD3, LMNB2 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and PLXDC1, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and PROK1, AREG, CEACAM5, SOD3, RET, CCL7 and MMP12, TMPRSS15, PTX3, COMP, POF1B, PGA4 and ITM2A, SPP1, PLXDC2, COMP, IL4R, TCL1A and PROK1, CRTAC1, SPP1, TCL1A, SOD3, L MNB2 and ADGRE2, PTX3, GDF15, POF1B, THBS4, ADGRE1 and EXTL1, NOTCH1, COMP, GDF15, PTX3, PGA4 and CEACAM5, PTX3, POF1B, THBS4, ADGRE5, PGA4 and NPY, PTX3, LMNB2, SOD3, CNTN4, PGA4 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, PLXD C1 and ITM2A, TMPRSS15, PTX3, GDF15, THBS4, ADGRE1 and IL4R, PTX3, COMP, HMCN2, POF1B, PGA4 and ADGRE1, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and C9, SPP1, PLXDC2, COMP, LMNB2, TCL1A and CLEC3B, SPP1, FCRL1, SOD3, ADGRE5, LMNB 2 and CEACAM16,TMPRSS15, PTX3, GDF15, COMP, PGA4 and ITM2A,PTX3, GDF15, THBS4, CLEC3B, ADGRE1 and TNC,GDF15, SPP1, PLXDC2, COMP, PROK1 and LMNB2,ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and TNC,PTX3, GDF15, ENPP6, THBS4, A DGRE1 and AGR3, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and SPON2, AREG, CEACAM5, RET, LPL, KRT19 and SPON2, PTX3, GDF15, RET, ADGRG2, BMP4 and ADGRE1, TMPRSS15, COMP, PTX3, PGA4, POF1B and NPY, PTX3, POF1B, FCRL1, SOD3, PGA4 and I TM2A, PTX3, POF1B, THBS4, FASLG, ITM2A and EXTL1, PTX3, POF1B, THBS4, EXTL1, PGA4 and ITM2A, SPP1, COMP, LMNB2, FCRL1, LPL and LBP, PTX3, GDF15, THBS4, EXTL1, ADGRE1 and ENPP6, SPP1, COMP, FCRL1, SOD3, CFP and LMNB2, PTX3, G DF15, THBS4, ADGRG2, ADGRE1 and IL4R, SPP1, COMP, LMNB2, FCRL1, TNC and CLEC3B, ADGRE1, KRT19, LMNB2, COMP, PTX3 and PGA4, PTX3, SPP1, ENPP6, COMP, TCL1A and ADGRE2, PTX3, GDF15, PLXDC2, THBS4, AGR3 and TNC, SPP1, ITGA11, FCRL1, SOD3, LMNB2 and PLXDC1, SPP1, COMP, LMNB2, FCRL1, PROK1 and SOD3, TMPRSS15, PTX3, GDF15, COMP, ADGRE1 and PGA4, SPP1, THBS4, LMNB2, ADGRE5, PROK1 and BAG3, SPP1, COMP, LMNB2, FCRL1, ADGRE1 and PTPRS, PTX3, ITGA11, POF1B, RET, SOD3 and PGA4, SPP1, COMP, FCRL1, ADGRE5, LPL and LMNB2, SPP1, COMP, LMNB2, FCRL1, SOD3 and CEACAM16, PTX3, GDF15, COMP, ADGRG2, ADGRE1 and THBS4, PTX3, COMP, POF1B, FCRL1, PGA4 and IL4R, PTX3, GDF15, THBS4, FA SLG, TMPRSS15 and ITM2A, TMPRSS15, PTX3, POF1B, THBS4, PGA4 and CFP, PTX3, GDF15, THBS4, ADGRG2, BMP4 and PROK1, PTX3, GDF15, COMP, EXTL1, PGA4 and NOTCH1, ADGRE1, LMNB2, THBS4, TMPRSS15, GDF15 and TNC, SPP1, COMP, LMNB2 , SOD3, FCRL1 and ASAH2, SPP1, COMP, FCRL1, ADGRE5, LMNB2 and TNC, SPP1, PLXDC2, COMP, LMNB2, FCRL1 and PLXDC1, SPP1, ADGRG2, FCRL1, SOD3, BAG3 and LMNB2, GSN, TMPRSS15, PGA4, PTX3, POF1B and SOD3, TMPRSS15, PTX3, THBS4, F ASLG, MMP12 and ITM2A, TMPRSS15, PTX3, GDF15, THBS4, CCL7 and ADGRE1, COMP, FCRL1, PTX3, GDF15, NOTCH1 and PGA4, SPP1, THBS4, LMNB2, ADGRE5, CLEC3B and PROK1, PTX3, GDF15, THBS4, ADGRG2, PROK1 and TCL1A, SPP1, COMP, LMNB 2. FCRL1, CLEC3B and BAG3, TMPRSS15, SPP1, FCRL1, SOD3, PLXDC1 and EDA2R, PTX3, GDF15, POF1B, THBS4, ADGRE5 and TNC, TMPRSS15, PTX3, THBS4, FASLG, GDF15 and AREG, SPP1, COMP, FCRL1, SOD3, TCL1A and LPL, PTX3, GDF15, THBS4 , FASLG, ADGRE1 and POF1B, TMPRSS15, PTX3, GDF15, THBS4, FASLG and TNC, PTX3, GDF15, THBS4, EXTL1, ITM2A and TNC, SPP1, LMNB2, FCRL1, SOD3, COMP and TMPRSS15, SPP1, LMNB2, SOD3, ADGRE5, FCRL1 and NT5C1A, PTX3, GDF15, COMP, THBS4, ADGRE1 and ITGA2, SPP1, PLXDC2, FCRL1, SOD3, ESM1 and BAG3, TMPRSS15, PTX3, SPP1, THBS4, AREG and FASLG, SPP1, COMP, LMNB2, FASLG, FCRL1 and TCL1A, SPP1, PLXDC2, COMP, LMNB2, PROK1 and BAG3, AREG, CEACAM5, PTX3, CD 48, CCL7 and IGSF3, SPP1, PLXDC2, COMP, LMNB2, PROK1 and DCC, SPP1, COMP, FCRL1, SOD3, LMNB2 and ADGRE1, AREG, CEACAM5, PTX3, CD48, CCL7 and NOTCH3, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and CDH23, SPP1, COMP, LMNB2, FCRL1, PLXD C2 and ESM1, AREG, CEACAM5, PTX3, CD48, CCL7 and PLXDC2, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and EXTL1, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and EDA2R, SPP1, PLXDC2, COMP, LMNB2, PROK1 and FCER2, AREG, CEACAM5, SOD3, RET, CCL7 and ENPP6, SPP1, LMNB2, FCRL1, SOD3, AGR3 and PLXDC1, SPP1, COMP, LMNB2, SOD3, TCL1A and PLXDC2, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and TCL1A, SPP1, PLXDC2, COMP, LMNB2, PROK1 and THBS4, SPP1, PLXDC2, COMP, LMNB2, PROK 1 and CCL7, SPP1, COMP, FCRL1, SOD3, LMNB2 and GCG, AREG, CEACAM5, SOD3, RET, CCL7 and EXTL1, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and ADGRG2, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and PLXDC1, SPP1, COMP, LMNB2, SOD3, TCL1A and ITM2A, P TX3, GDF15, POF1B, THBS4, ADGRE1 and PKD1, AREG, CEACAM5, SOD3, RET, CCL7 and ADAMTS8, TMPRSS15, PTX3, COMP, POF1B, PGA4 and ESM1, PTX3, LMNB2, SOD3, CNTN4, PGA4 and ADGRE1, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and SPON2, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ADGRE5, PTX3, GDF15, POF1B, THBS4, ADGRE1 and CDH23, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and TMPRSS15, PTX3, COMP, HMCN2, POF1B, PGA4 and PLXDC1, AREG, CEACAM5, SOD3, RET, CCL7 and GN AS,AREG,CEACAM5,PLXDC2,COMP,ADGRE2 and CLEC3B,CRTAC1,SPP1,TCL1A,SOD3,LMNB2 and ADGRE1,SPP1,COMP,LMNB2,SOD3,TCL1A and SELL,SPP1,PLXDC2,COMP,LMNB2,PROK1 and PLXDC1,AREG,CEACAM5,PTX3,CD48,CCL7 and POF 1B, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and TCL1A, AREG, CEACAM5, SOD3, RET, CCL7 and POF1B, PTX3, GDF15, POF1B, THBS4, ADGRE1 and TNC, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and IL6, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and TCL1A, ARE G, CEACAM5, PTX3, CD48, CCL7 and ITGAM, SPP1, PLXDC2, COMP, LMNB2, PROK1 and SOD3, SPP1, PLXDC2, COMP, LMNB2, PROK1 and IL4R, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and GNAS, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and PTPRS, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and PLXDC1, SPP1, COMP, FCRL1, SOD3, LMNB2 and TNC, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ITGA2, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and SPP1, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and CNTN4, S PP1, COMP, FCRL1, SOD3, LMNB2 and C9, NOTCH1, COMP, GDF15, PTX3, PGA4 and ADGRE1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and CNTN4, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and TCL1A, AREG, CEACAM5, PTX3, CD48, CCL7 and ASAH2, AREG, CEA CAM5, SOD3, RET, CCL7 and ITGAM, AREG, CEACAM5, SOD3, RET, CCL7 and ITM2A, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and ITGA11, AREG, CEACAM5, RET, LPL, KRT19 and PTPRS, AREG, CEACAM5, SOD3, RET, CCL7 and IGSF3, SPP1, LMNB2, FCRL1 , SOD3, PLXDC1 and PLXDC2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and MEGF9, PTX3, POF1B, FCRL1, SOD3, PGA4 and PLXDC1, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and TMPRSS15, AREG, CEACAM5, SOD3, RET, CCL7 and CFP, PTX3, POF1B, THBS4, EXTL1, PGA4 and ADGRE1, SPP1, LMNB2, FCRL1, SOD3, ITGB1 and PLXDC1, PTX3, POF1B, THBS4, ADGRE5, PGA4 and ITM2A, SPP1, COMP, LMNB2, SOD3, ADGRE1 and PROK1, TMPRSS15, PTX3, COMP, POF1B, PGA4 and CKAP4, TMPRSS15, PTX3, COMP , POF1B, PGA4 and ADGRE1, TMPRSS15, PTX3, COMP, POF1B, PGA4 and THBS4, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and BAG3, TMPRSS15, PTX3, COMP, POF1B, PGA4 and NPY, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and PROK1, PTX3, GDF15, POF1B, T HBS4, ADGRE1 and AREG, SPP1, COMP, LMNB2, SOD3, TCL1A and CEACAM16, SPP1, PLXDC2, COMP, LMNB2, PROK1 and MMP12, AREG, CEACAM5, SOD3, RET, CCL7 and DLK1, SPP1, COMP, LMNB2, SOD3, TCL1A and CNTN4, AREG, CEACAM5, PTX3, CD48, CCL7 and CDH23, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ADGRE5, NOTCH1, COMP, GDF15, PTX3, PGA4 and ITM2A, PTX3, POF1B, THBS4, EXTL1, PGA4 and SOD3, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and ITGA11, SPP1, COMP, FCRL1, SOD3, LMNB2 with NOS2, PTX3, GDF15, POF1B, THBS4, ADGRE1 and LMNB2, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and THBS4, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and AGR3, SPP1, PLXDC2, COMP, LMNB2, PROK1 and LPL, GDF15, SPP1, PLXDC2, COMP, PROK 1 and ADAMTS8, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and CEACAM16, PTX3, GDF15, POF1B, THBS4, ADGRE1 and CFP, SPP1, COMP, LMNB2, SOD3, TCL1A and MEGF9, SPP1, PLXDC2, COMP, LMNB2, PROK1 and GNAS, SPP1, PLXDC2, COMP, LMNB2, PROK 1 and AGR3, AREG, CEACAM5, SOD3, RET, CCL7 and PTPRS, TMPRSS15, PTX3, COMP, POF1B, PGA4 and IL4R, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ESM1, SPP1, LMNB2, FCRL1, SOD3, AGR3 and PLXDC2, TMPRSS15, PTX3, COMP, POF1B, PGA4 and IGFBP1,AREG,CEACAM5,RET,LPL,KRT19 and IL4R,AREG,CEACAM5,SOD3,RET,CCL7 and IL4R,SPP1,LMNB2,FCRL1,SOD3,PLXDC1 and GCG,SPP1,COMP,FCRL1,SOD3,LMNB2 and PLXDC1,SPP1,COMP,LMNB2,FCRL1,PLXDC2 and TNC,PTX3, POF1B, THBS4, EXTL1, PGA4 and CLEC3B, SPP1, COMP, LMNB2, SOD3, ADGRE1 and TCL1A, TMPRSS15, PTX3, COMP, POF1B, PGA4 and GDF15, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and BMP4, PTX3, GDF15, THBS4, ADGRE5, ADGRE1 and TNC, PTX3, POF1B, THBS4, EXTL1, PGA4 and PCDH7, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and FAP, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and BMP4, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and AREG, PTX3, GDF15, THBS4, EXTL1, ADGRE1 and TNC, SPP1, LMNB 2. FCRL1, SOD3, PLXDC1 and BAG3, AREG, CEACAM5, SOD3, RET, CCL7 and SPP1, SPP1, COMP, FCRL1, SOD3, LMNB2 and PLXDC2, SPP1, COMP, LMNB2, SOD3, TCL1A and CLEC3B, SPP1, COMP, LMNB2, SOD3, ADGRE1 and LPL, AREG, CEACAM5, PTX3, C D48, CCL7 and CLEC3B, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and CDH23, SPP1, PLXDC2, COMP, LMNB2, TCL1A and IGFBP1, PTX3, GDF15, RET, ADGRG2, BMP4 and FASLG, AREG, CEACAM5, PTX3, CD48, CCL7 and ENPP6, AREG, CEACAM5, PTX3, CD48 , CCL7 and ITGB1, SPP1, COMP, LMNB2, SOD3, ADGRE1 and CFP, SPP1, PLXDC2, COMP, LMNB2, TCL1A and ADGRE5, PTX3, POF1B, FCRL1, SOD3, PGA4 and TMPRSS15, NOTCH1, COMP, GDF15, PTX3, PGA4 and FCER2, PTX3, COMP, HMCN2, POF1B, PGA4 with ITM2A, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and GNAS, PTX3, LMNB2, SOD3, CNTN4, PGA4 and RET, SPP1, COMP, LMNB2, FCRL1, LPL and PLXDC2, SPP1, PLXDC2, COMP, LMNB2, TCL1A and POF1B, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and DCC, SP P1, COMP, FCRL1, SOD3, LMNB2 and FCER2, SPP1, COMP, FCRL1, SOD3, LMNB2 and SERPINA1, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and FCRL1, NOTCH1, COMP, GDF15, PTX3, PGA4 and DLK1, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and ITGB1, AREG, C EACAM5, SOD3, RET, CCL7 and THBS4, PTX3, POF1B, THBS4, ADGRE5, PGA4 and ENPP6, AREG, CEACAM5, PTX3, CD48, CCL7 and DLK1, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and COMP, SPP1, PLXDC2, COMP, LMNB2, PROK1 and POF1B, PTX3, GDF15, E NPP6, THBS4, ADGRE1 and BMP4, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and TCL1A, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and AREG, PTX3, GDF15, POF1B, THBS4, ADGRE1 and PTPRS, SPP1, COMP, LMNB2, FCRL1, SOD3 and CDH23, TMPRSS15, PTX3, GDF15, THBS4, ADGRE1 and LMNB2, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ANGPTL4, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ENPP6, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and CNTN4, SPP1, PLXDC2, COMP, LMNB2, PROK1 and PGA4, AREG , CEACAM5, SOD3, RET, CCL7 and ITGB1, SPP1, COMP, LMNB2, FCRL1, LPL and TCL1A, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and CLEC3B, SPP1, PLXDC2, COMP, IL4R, TCL1A and DCC, AREG, CEACAM5, SOD3, RET, CCL7 and ESM1, PTX3, GDF15, COMP , ADGRG2, ADGRE1 and PGA4, SPP1, PLXDC2, COMP, LMNB2, PROK1 and NOS2, AREG, CEACAM5, SOD3, RET, CCL7 and C9, TMPRSS15, PTX3, GDF15, THBS4, ADGRE1 and PGA4, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and FCRL1, AREG, CEACAM5, SOD 3. RET, CCL7 and EDA2R, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and BAG3, NOTCH1, COMP, GDF15, PTX3, PGA4 and ADGRE2, AREG, CEACAM5, SOD3, RET, CCL7 and GCG, SPP1, COMP, LMNB2, SOD3, TCL1A and PLXDC1, SPP1, COMP, LMNB2, SOD3, TCL1 A and ITGB1, PTX3, POF1B, THBS4, FASLG, ITM2A and PCDH7, TMPRSS15, COMP, PTX3, PGA4, POF1B and FASLG, AREG, CEACAM5, SOD3, RET, CCL7 and SPON2, SPP1, COMP, LMNB2, FCRL1, LPL and IFNL1, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and IT GA2,AREG,CEACAM5,SOD3,RET,CCL7 and FAP,ADGRE1,GDF15,PTX3,THBS4,ADGRG2 and RET,SPP1,PLXDC2,COMP,LMNB2,PROK1 and TNC,SPP1,LMNB2,FCRL1,SOD3,MEGF9 and LPL,AREG,CEACAM5,PLXDC2,COMP,ADGRE2 and GRK5,AREG , CEACAM5, SOD3, RET, CCL7 and CDH23, SPP1, COMP, LMNB2, FCRL1, LPL and GSN, SPP1, PLXDC2, COMP, LMNB2, PROK1 and SERPINA1, TMPRSS15, COMP, PTX3, PGA4, POF1B and FCRL1, PTX3, POF1B, THBS4, EXTL1, PGA4 and PROK1, AREG, CEAC AM5, PTX3, CD48, CCL7 and ADGRE1, AREG, CEACAM5, SOD3, RET, CCL7 and IFNL1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and ADGRE1, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and CDH23, SPP1, COMP, LMNB2, SOD3, TCL1A and ADGRE5, SPP1, COMP, LM NB2, FCRL1, SOD3 and MEGF9, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and C9, PTX3, GDF15, POF1B, THBS4, ADGRE1 and NPY, SPP1, PLXDC2, COMP, LMNB2, PROK1 and IGDCC4, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and PROK1, TMPRSS15, PTX3, GDF1 5. COMP, PGA4 and ENPP6, SPP1, COMP, LMNB2, FCRL1, LPL and CLEC3B, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and NOTCH3, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and CEACAM16, PTX3, GDF15, THBS4, CLEC3B, ADGRE1 and BMP4, TMPRSS15, PTX3 , GDF15, THBS4, PGA4 and ITM2A, TMPRSS15, PTX3, GDF15, COMP, PGA4 and C9, TMPRSS15, COMP, PTX3, PGA4, POF1B and TNC, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and TNFRSF10B, PTX3, GDF15, POF1B, THBS4, ADGRE1 and ITGA11, PTX3, G DF15, THBS4, ADGRG2, ADGRE1 and TNC, AREG, CEACAM5, SOD3, RET, CCL7 and ADGRE5, PTX3, GDF15, POF1B, THBS4, ADGRE1 and LPL, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and THBS4, PTX3, GDF15, POF1B, THBS4, ADGRE1 and ITM2A, PTX3, GDF 15, THBS4, EXTL1, ADGRE1 and ITM2A, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and PROK1, PTX3, LMNB2, SOD3, CNTN4, PGA4 and MEGF9, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and PGA4, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and TCL1A, SPP1, COMP, LMNB2, FCRL1, ADGRE1 and TCL1A, PTX3, COMP, POF1B, FCRL1, PGA4 and TMPRSS15, NOTCH1, COMP, GDF15, PTX3, PGA4 and AGR3, PTX3, GDF15, ENPP6, THBS4, ADGRE1 and AREG, SPP1, PLXDC2, COMP, LMNB2, PROK1 and PCDH7, PTX3, GDF15, P OF1B, THBS4, ADGRE1 and ITGA2, SPP1, COMP, LMNB2, SOD3, TCL1A and FCER2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and IL6, SPP1, THBS4, LMNB2, ADGRE5, PROK1 and PLXDC2, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and IL4R, SPP1, PLXDC2, COM P, LMNB2, PROK1 and PTPRS, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and DLK1, PTX3, GDF15, ENPP6, THBS4, ADGRE1 and ITGA11, AREG, CEACAM5, PTX3, CD48, CCL7 and ADAMTS8, AREG, CEACAM5, SOD3, RET, CCL7 and BAG3, SPP1, COMP, FCRL1, S OD3, LMNB2 and ITGA2, PTX3, GDF15, COMP, ADGRG2, ADGRE1 and TCL1A, PTX3, POF1B, THBS4, ADGRE5, PGA4 and GSN, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and DCC, AREG, CEACAM5, PTX3, CD48, CCL7 and AGR3, AREG, CEACAM5, PTX3, CD48, CCL7 and GDF15, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and ADGRE5, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and TCL1A, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ITGA2, TMPRSS15, COMP, PTX3, PGA4, POF1B and ITM2A, SPP1, LMNB2, FCRL1, SO D3, ADGRE5 and MEGF9, PTX3, GDF15, POF1B, THBS4, ADGRE1 and GSN, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and BAG3, AREG, CEACAM5, SOD3, RET, CCL7 and SERPINA1, PTX3, GDF15, POF1B, THBS4, ADGRE1 and ADGRE5, SPP1, COMP, FCRL1, SOD3, LMNB2 and LPL, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and ADGRE1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and CFP, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and ITM2A, TMPRSS15, PTX3, POF1B, THBS4, PGA4 and SOD3, NOTCH1, COMP, GDF15, PTX 3. PGA4 and ADAMTS8, AREG, CEACAM5, RET, LPL, KRT19 and C9, AREG, CEACAM5, RET, LPL, KRT19 and ESM1, AREG, CEACAM5, SOD3, RET, CCL7 and TNFRSF10B, PTX3, GDF15, THBS4, CLEC3B, ADGRE1 and TCL1A, SPP1, FCRL1, SOD3, ADGRE5, LM NB2 and GCG, SPP1, COMP, FCRL1, SOD3, LMNB2 and ITIH3, PTX3, GDF15, POF1B, THBS4, ADGRE1 and BMP4, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and IFNL1, AREG, CEACAM5, SOD3, RET, CCL7 and IGFBP1, SPP1, COMP, LMNB2, SOD3, FCRL1 and I TM2A,TMPRSS15, PTX3, GDF15, COMP, PGA4 and BMP4, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ADAMTS8, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and RET, TMPRSS15, PTX3, GDF15, THBS4, PGA4 and CLEC3B, ADGRE1, LMNB2, THBS4, TMPRSS 15, GDF15 and CLEC3B, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and FCER2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and TNFRSF10B, AREG, CEACAM5, PTX3, CD48, CCL7 and IFNL1, SPP1, PLXDC2, COMP, IL4R, TCL1A and LMNB2, PTX3, GDF15, THBS4, E XTL1, ADGRE1 and AGR3, SPP1, COMP, LMNB2, SOD3, TCL1A and AREG, AREG, CEACAM5, PTX3, CD48, CCL7 and MMP12, AREG, CEACAM5, SOD3, RET, CCL7 and DCC, PTX3, GDF15, THBS4, CLEC3B, ADGRE1 and POF1B, SPP1, COMP, LMNB2, SOD3, TCL1A with ASAH2, SPP1, COMP, LMNB2, FCRL1, LPL and PROK1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and DLK1, SPP1, PLXDC2, COMP, LMNB2, PROK1 and FGF21, SPP1, PLXDC2, SOD3, IL4R, BAG3 and LMNB2, SPP1, COMP, FCRL1, SOD3, LMNB2 and GRK5, ARE G, CEACAM5, RET, LPL, KRT19 and TMPRSS15, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and SOD3, PTX3, GDF15, ENPP6, THBS4, ADGRE1 and TNC, AREG, CEACAM5, PTX3, CD48, CCL7 and FAP, PTX3, COMP, POF1B, FCRL1, PGA4 and CLEC3B, SPP1, LMNB 2. SOD3, ADGRE5, TCL1A and IFNL1, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and CLEC3B, NOTCH1, COMP, GDF15, PTX3, PGA4 and TCL1A, TMPRSS15, PTX3, GDF15, COMP, PGA4 and FCRL1, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and ADGRG2, SPP1, LMN B2, FCRL1, SOD3, PLXDC1 and AREG, SPP1, LMNB2, FCRL1, SOD3, TCL1A and PROK1, PTX3, GDF15, COMP, ADGRG2, ADGRE1 and DCC, PTX3, GDF15, THBS4, EXTL1, ADGRE1 and BMP4, SPP1, PLXDC2, COMP, LMNB2, PROK1 and PKD1, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and FAP, AREG, CEACAM5, PTX3, CD48, CCL7 and PTPRS, PTX3, GDF15, COMP, ADGRG2, ADGRE1 and RET, SPP1, COMP, LMNB2, FCRL1, LPL and PTPRS, TMPRSS15, PTX3, COMP, POF1B, PGA4 and FASLG, SPP1, THBS4, LMNB2, ADGRE5, PROK1 and SOD3, GSN, TMPRSS15, PGA4, PTX3, POF1B and COMP, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and PGA4, TMPRSS15, PTX3, COMP, POF1B, PGA4 and IFNL1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and NT5C1A, SPP1, PLXDC2, COMP, L MNB2, TCL1A and CNTN1, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and ADGRE5, PTX3, LMNB2, SOD3, CNTN4, PGA4 and ITM2A, PTX3, COMP, HMCN2, POF1B, PGA4 and NOTCH1, SPP1, LMNB2, FCRL1, SOD3, ITGB1 and COMP, AREG, CEACAM5, PLXDC2, COM P, ADGRE2 and AGR3, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and SOD3, AREG, CEACAM5, RET, LPL, KRT19 and PLXDC2, NOTCH1, COMP, GDF15, PTX3, PGA4 and PCDH7, GDF15, SPP1, PLXDC2, COMP, PROK1 and FCER2, AREG, CEACAM5, PTX3, SPP1, PLXDC2 and ADGRE5, PTX3, POF1B, FCRL1, SOD3, PGA4 and EXTL1, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and PROK1, PTX3, POF1B, THBS4, EXTL1, PGA4 and BAG3, SPP1, COMP, LMNB2, FCRL1, ADGRE1 and LPL, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and NOTCH1, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and ITIH3, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and GDF15, PTX3, COMP, POF1B, FCRL1, PGA4 and ITM2A, TMPRSS15, PTX3, COMP, POF1B, PGA4 and NT5C1A, SPP1, PLXDC2, COMP, LMNB2, TC L1A and TNC,AREG,CEACAM5,PLXDC2,COMP,ADGRE2 and PTX3,TMPRSS15,PTX3,GDF15,THBS4,PGA4 and COMP,SPP1,PLXDC2,COMP,LMNB2,TCL1A and VSIG4,SPP1,COMP,LMNB2,SOD3,TCL1A and TNC,PTX3,COMP,POF1B,FCRL1,PGA4 and PL XDC1, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and ADGRE1, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and AREG, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and FASLG, NOTCH1, COMP, GDF15, PTX3, PGA4 and PKD1, PTX3, GDF15, POF1B, THBS4, ADGRE1 and CEACAM16,TMPRSS15,PTX3,GDF15,THBS4,ADGRE1 and GNAS,SPP1,LMNB2,FCRL1,SOD3,PLXDC1 and TCL1A,SPP1,PLXDC2,COMP,LMNB2,PROK1 and ASAH2,SPP1,PLXDC2,COMP,IL4R,TCL1A and DLK1,SPP1,FCRL1,SOD3,ADGRE5,LMN B2 and PGA4, SPP1, COMP, FCRL1, ADGRE5, LMNB2 and PROK1, AREG, CEACAM5, RET, LPL, KRT19 and ENPP6, PTX3, LMNB2, SOD3, CNTN4, PGA4 and BMP4, SPP1, PLXDC2, COMP, LMNB2, PROK1 and IGSF3, TMPRSS15, PTX3, GDF15, THBS4, ADGRE1 and PLXDC1, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and CLEC3B, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and CLEC3B, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and ITGA11, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ITGB1, AREG, CEACAM5, SOD3, RET, CCL 7 and NTRK2, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and PROK1, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and PGA4, SPP1, COMP, LMNB2, FCRL1, SOD3 and AREG, PTX3, COMP, HMCN2, POF1B, PGA4 and FASLG, PTX3, LMNB2, SOD3, CNTN4, PGA4 and TNC, SPP1 , COMP, LMNB2, FCRL1, PLXDC2 and NOS2, SPP1, PLXDC2, COMP, LMNB2, TCL1A and ADGRG2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and NT5C1A, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and FAP, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and RBFOX3, SPP 1. COMP, LMNB2, SOD3, FCRL1 and VSIG4, PTX3, COMP, HMCN2, POF1B, PGA4 and LMNB2, PTX3, POF1B, FCRL1, SOD3, PGA4 and ADGRE5, AREG, CEACAM5, PTX3, CD48, CCL7 and TMPRSS15, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and CNTN4, PTX3, GD F15, THBS4, ADGRG2, ADGRE1 and FASLG, SPP1, COMP, LMNB2, SOD3, FCRL1 and ADGRG2, SPP1, ITGA11, FCRL1, SOD3, LMNB2 and PLXDC2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and BMP4, TMPRSS15, PTX3, COMP, POF1B, PGA4 and CCL7, SPP1, LM NB2, FCRL1, SOD3, PLXDC1 and GRK5, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and NOS2, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and GRK5, AREG, CEACAM5, SOD3, RET, CCL7 and TMPRSS15, SPP1, COMP, LMNB2, FCRL1, PROK1 and ADGRG2, SPP1, COMP , FCRL1, SOD3, LMNB2 and CCL7, AREG, CEACAM5, SOD3, RET, CCL7 and ITGA11, TMPRSS15, PTX3, POF1B, THBS4, PGA4 and ITM2A, TMPRSS15, PTX3, COMP, POF1B, PGA4 and TNFRSF10B, AREG, CEACAM5, RET, LPL, KRT19 and ADGRE1, SPP1, LMN B2, SOD3, ADGRE5, TCL1A and BAG3, SPP1, ITGA11, FCRL1, SOD3, LMNB2 and TCL1A, TMPRSS15, PTX3, GDF15, THBS4, FGF21 and ADGRE1, SPP1, COMP, LMNB2, SOD3, TCL1A and GRK5, PTX3, POF1B, THBS4, EXTL1, PGA4 and PTPRS, SPP1, LMNB2 , FCRL1, SOD3, PLXDC1 and PGA4, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and CEACAM16, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and AGR3, PTX3, GDF15, POF1B, THBS4, ADGRE1 and IL6, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and TNC, SPP1, COMP, FCR L1, ADGRE5, LMNB2 and PLXDC1, PTX3, POF1B, FCRL1, SOD3, PGA4 and NPY, PTX3, POF1B, THBS4, EXTL1, PGA4 and LPL, SPP1, COMP, FCRL1, SOD3, LMNB2 and BAG3, TMPRSS15, SPP1, FCRL1, SOD3, PLXDC1 and CKAP4, TMPRSS15, PTX3, POF1B, T HBS4, PGA4 and ITGA11, TMPRSS15, PTX3, GDF15, COMP, PGA4 and MMP12, NOTCH1, COMP, GDF15, PTX3, PGA4 and BMP4, SPP1, COMP, LMNB2, SOD3, TCL1A and DLK1, NOTCH1, COMP, GDF15, PTX3, PGA4 and PLXDC1, SPP1, COMP, LMNB2, FCRL1, S OD3 and PKD1, SPP1, COMP, FCRL1, SOD3, LMNB2 and PGA4, TMPRSS15, PTX3, COMP, POF1B, PGA4 and CDH23, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and ITM2A, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and CFP, AREG, CEACAM5, PTX3, CD48, CCL 7 and ITGA2, AREG, CEACAM5, RET, LPL, KRT19 and PLXDC1, PTX3, COMP, HMCN2, POF1B, PGA4 and LPL, SPP1, COMP, FCRL1, SOD3, LMNB2 and IFNL1, SPP1, PLXDC2, COMP, LMNB2, TCL1A and IL6, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and IL4R, T MPRSS15, COMP, PTX3, PGA4, POF1B and GDF15, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and LPL, TMPRSS15, COMP, PTX3, PGA4, POF1B and LMNB2, SPP1, THBS4, LMNB2, ADGRE5, CLEC3B and FCRL1, TMPRSS15, PTX3, COMP, POF1B, PGA4 and PROK1 ,ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and ADGRE2, NOTCH1, COMP, GDF15, PTX3, PGA4 and EXTL1, SPP1, COMP, LMNB2, FCRL1, SOD3 and AGR3, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and DCC, GDF15, SPP1, PLXDC2, COMP, PROK1 and BAG3, AR EG, CEACAM5, PLXDC2, COMP, ADGRE2 and C9, AREG, CEACAM5, SOD3, RET, CCL7 and PLXDC2, PTX3, GDF15, COMP, ADGRG2, ADGRE1 and ADGRE2, SPP1, PLXDC2, COMP, LMNB2, PROK1 and CLEC3B, TMPRSS15, SPP1, FCRL1, SOD3, PLXDC1 and PGA4 ,AREG,CEACAM5,PTX3,CD48,CCL7 and TNFRSF10B,AREG,CEACAM5,SOD3,RET,CCL7 and NOTCH3,TMPRSS15,PTX3,GDF15,THBS4,ADGRE1 and POF1B,SPP1,PLXDC2,COMP,LMNB2,TCL1A and ITGA11,PTX3,SPP1,ENPP6,COMP,TCL1A and A DGRE5, PTX3, POF1B, FCRL1, SOD3, PGA4 and ADGRE2, PTX3, ITGA11, POF1B, RET, SOD3 and TNC, PTX3, GDF15, THBS4, CLEC3B, ADGRE1 and LMNB2, SPP1, PLXDC2, SOD3, IL4R, BAG3 and CEACAM16, SPP1, COMP, LMNB2, FCRL1, ADGRE1 and MMP1 2, NOTCH1, COMP, GDF15, PTX3, PGA4 and POF1B, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and SELL, TMPRSS15, COMP, PTX3, PGA4, POF1B and CLEC3B, TMPRSS15, PTX3, COMP, POF1B, PGA4 and SOD3, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and FASL G, PTX3, GDF15, POF1B, THBS4, ADGRE1 and SPON2, PTX3, ITGA11, POF1B, RET, SOD3 and LMNB2, SPP1, LMNB2, FCRL1, SOD3, TCL1A and ITGA2, SPP1, PLXDC2, COMP, LMNB2, TCL1A and FASLG, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and IL6, P TX3, POF1B, THBS4, EXTL1, PGA4 and IFNL1, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and ITIH3, PTX3, GDF15, THBS4, ADGRG2, PROK1 and ADGRE2, AREG, CEACAM5, SOD3, RET, CCL7 and ANGPTL4, PTX3, COMP, HMCN2, POF1B, PGA4 and NPY, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and COMP, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ESM1, TMPRSS15, COMP, PTX3, PGA4, POF1B and PCDH7, SPP1, LMNB2, FCRL1, SOD3, TCL1A and CNTN4, SPP1, COMP, FCRL1, ADGRE5, LMNB2 and SOD3, SPP1, LM NB2, FCRL1, SOD3, ADGRE1 and ITGA2, ADGRE1, LMNB2, THBS4, TMPRSS15, GDF15 and CFP, PTX3, GDF15, PLXDC2, THBS4, AGR3 and ITM2A, SPP1, COMP, FCRL1, SOD3, LMNB2 and NPY, PTX3, COMP, POF1B, FCRL1, PGA4 and PCDH7, PTX3, POF1B, FCRL1, SOD3, PGA4 and PCDH7, SPP1, PLXDC2, COMP, LMNB2, TCL1A and GDF15, TMPRSS15, PTX3, GDF15, COMP, PGA4 and PKD1, SPP1, PLXDC2, COMP, IL4R, TCL1A and CKAP4, TMPRSS15, PTX3, COMP, POF1B, PGA4 and FGF21, SPP1, LMNB2, FCR L1, SOD3, PLXDC1 and GSN, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and TNC, SPP1, PLXDC2, COMP, LMNB2, TCL1A and LPL, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and PLXDC2, SPP1, PLXDC2, COMP, IL4R, TCL1A and PGA4, SPP1, COMP, LMNB2, FCRL1, SOD3 and GNAS, PTX3, GDF15, ENPP6, THBS4, ADGRE1 and POF1B, SPP1, PLXDC2, COMP, IL4R, TCL1A and THBS4, TMPRSS15, PTX3, COMP, POF1B, PGA4 and MMP12, TMPRSS15, PTX3, GDF15, COMP, PGA4 and GNAS, SPP1, COMP, LMNB2, SOD3, TCL1A with PTX3,TMPRSS15,PTX3,COMP,POF1B,PGA4 and CFP,AREG,CEACAM5,RET,LPL,KRT19 and ITGA2,SPP1,COMP,LMNB2,SOD3,TCL1A and C9,PTX3,POF1B,THBS4,EXTL1,PGA4 and GSN,AREG,CEACAM5,PTX3,CD48,CCL7 and CNTN4,SPP1,CO MP, FCRL1, SOD3, LMNB2 and ENPP6, NOTCH1, COMP, GDF15, PTX3, PGA4 and FCRL1, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and SERPINA1, AREG, CEACAM5, PTX3, CD48, CCL7 and C9, AREG, CEACAM5, PTX3, CD48, CCL7 and PLXDC1, AREG, CEACAM5 , SOD3, RET, CCL7 and PTX3, ADGRE1, GDF15, PTX3, THBS4, ADGRG2 and NOS2, SPP1, PLXDC2, COMP, LMNB2, FCRL1 and ADGRE1, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and TNC, PTX3, POF1B, THBS4, EXTL1, PGA4 and TMPRSS15, AREG, CEACAM5, R ET, LPL, KRT19 and IFNL1, TMPRSS15, COMP, PTX3, PGA4, POF1B and DLK1, SPP1, COMP, LMNB2, SOD3, ADGRE1 and PLXDC1, PTX3, COMP, POF1B, FCRL1, PGA4 and MEGF9, SPP1, PLXDC2, COMP, LMNB2, TCL1A and BAG3, SPP1, COMP, FCRL1, ADGR E5, LMNB2 and PLXDC2, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and IL4R, SPP1, COMP, FCRL1, SOD3, LMNB2 and ESM1, PTX3, GDF15, THBS4, ADGRE5, ADGRE1 and CFP, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and ITGA11, TMPRSS15, PTX3, COMP, POF1 B, PGA4 and GRK5, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and CLEC3B, SPP1, LMNB2, FCRL1, SOD3, COMP and EXTL1, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and CFP, SPP1, LMNB2, FCRL1, SOD3, TCL1A and THBS4, SPP1, COMP, LMNB2, FCRL1, SOD3 and PCDH7, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and IFNL1, SPP1, LMNB2, SOD3, ADGRE5, FCRL1 and NOS2, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and ENPP6, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ITGA11, AREG, CEACAM5, RET, LPL, KRT19 and EXTL1, SPP1, LMNB2, SOD3, ADGRE5, PLXDC1 and ITM2A, PTX3, POF1B, THBS4, ADGRE5, PGA4 and TNC, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and ADAMTS8, TMPRSS15, PTX3, COMP, POF1B, PGA4 and ENPP6, SPP1, COMP, LMNB2, SOD3, FCRL1 and DLK1, SPP1, PLXDC2, COMP, LMNB2, PROK1 and ENPP6, TMPRSS15, COMP, PTX3, PGA4, POF1B and PROK1, PTX3, GDF15, POF1B, THBS4, ADGRE1 and IL4R, TMPRSS15, PTX3, GDF15, THBS4, FASLG and GNAS, SPP1, PLXDC2, COMP, LMNB2, PROK1 CNTN5, AREG, CEACAM5, RET, LPL, KRT19 and COMP, NOTCH1, COMP, GDF15, PTX3, PGA4 and ASAH2, PTX3, GDF15, RET, ADGRG2, BMP4 and AGR3, TMPRSS15, PTX3, POF1B, THBS4, PGA4 and ADGRE1, TMPRSS15, PTX3, COMP, POF1B, PGA4 and ASA H2, SPP1, LMNB2, FCRL1, SOD3, PLXDC2 and ESM1, TMPRSS15, PTX3, GDF15, COMP, PGA4 and FGF21, PTX3, GDF15, RET, ADGRG2, BMP4 and PROK1, SPP1, PLXDC2, SOD3, IL4R, BAG3 and ESM1, SPP1, COMP, LMNB2, SOD3, TCL1A and ADGRG2, TMPR SS15, PTX3, POF1B, THBS4, PGA4 and BMP4, SPP1, COMP, LMNB2, FCRL1, LPL and GNAS, AREG, CEACAM5, PTX3, CD48, CCL7 and FCRL1, AREG, CEACAM5, SOD3, RET, CCL7 and ITGA2, SPP1, LMNB2, SOD3, ADGRE5, FCRL1 and ITM2A, SPP1, LMNB2, F CRL1, SOD3, ADGRE1 and TMPRSS15, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and LBP, SPP1, COMP, FCRL1, CLEC3B, LMNB2 and ITIH3, SPP1, COMP, LMNB2, FCRL1, PLXDC2 and GCG, SPP1, LMNB2, FCRL1, SOD3, PLXDC2 and GCG, AREG, CEACAM5 , SOD 3. RET, CCL7 and GRK5, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and CD48, TMPRSS15, COMP, PTX3, PGA4, POF1B and CNTN5, SPP1, LMNB2, FCRL1, SOD3, TCL1A and ITM2A, PTX3, GDF15, POF1B, THBS4, ADGRE1 and BAG3, PTX3, POF1B, THBS4, FASL G, ITM2A and ADGRG2, PTX3, LMNB2, SOD3, CNTN4, PGA4 and ESM1, SPP1, COMP, LMNB2, FCRL1, LPL and ITM2A, AREG, CEACAM5, PTX3, CD48, CCL7 and BMP4, AREG, CEACAM5, PTX3, CD48, CCL7 and EDA2R, PTX3, COMP, HMCN2, POF1B, PGA4 and CNT N4, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and FASLG, TMPRSS15, COMP, PTX3, PGA4, POF1B and AREG, PTX3, LMNB2, SOD3, CNTN4, PGA4 and GRK5, SPP1, THBS4, LMNB2, ADGRE5, PROK1 and ENPP6, or PTX3, GDF15, THBS4, ADGRG2, PROK1 and BMP4.
优选地，所述6markers组合为：SPP1、PLXDC2、SOD3、IL4R、BAG3与PROK1,AREG、CEACAM5、PTX3、CD48、CCL7与IGFBP1,SPP1、PLXDC2、COMP、LMNB2、PROK1与TCL1A,SPP1、LMNB2、FCRL1、SOD3、PLXDC2与BAG3,SPP1、COMP、LMNB2、SOD3、TCL1A与PROK1,SPP1、LMNB2、FCRL1、SOD3、MEGF9与PROK1,SPP1、LMNB2、SOD3、ADGRE5、TCL1A与PROK1,AREG、CEACAM5、PLXDC2、COMP、ADGRE2与ADAMTS8,SPP1、COMP、FCRL1、SOD3、LMNB2与TCL1A,SPP1、LMNB2、FCRL1、SOD3、ADGRE1与PLXDC1,SPP1、COMP、LMNB2、FCRL1、PLXDC2与PROK1,AREG、CEACAM5、SOD3、RET、CCL7与MMP12,TMPRSS15、PTX3、COMP、POF1B、PGA4与ITM2A,SPP1、PLXDC2、COMP、IL4R、TCL1A与PROK1,CRTAC1、SPP1、TCL1A、SOD3、LMNB2与ADGRE2,PTX3、GDF15、POF1B、THBS4、ADGRE1与EXTL1,NOTCH1、COMP、GDF15、PTX3、PGA4与CEACAM5,PTX3、POF1B、THBS4、ADGRE5、PGA4与NPY,PTX3、LMNB2、SOD3、CNTN4、PGA4与TCL1A,SPP1、LMNB2、FCRL1、SOD3、PLXDC1与ITM2A,TMPRSS15、PTX3、GDF15、THBS4、ADGRE1与IL4R,PTX3、COMP、HMCN2、POF1B、PGA4与ADGRE1,SPP1、LMNB2、FCRL1、SOD3、ADGRE5与C9,SPP1、PLXDC2、COMP、LMNB2、TCL1A与CLEC3B,SPP1、FCRL1、SOD3、ADGRE5、LMNB2与CEACAM16,TMPRSS15、PTX3、GDF15、COMP、PGA4与ITM2A,PTX3、GDF15、THBS4、CLEC3B、ADGRE1与TNC,GDF15、SPP1、PLXDC2、COMP、PROK1与LMNB2,ADGRE1、GDF15、PTX3、THBS4、ADGRG2与TNC,PTX3、GDF15、ENPP6、THBS4、ADGRE1与AGR3,AREG、CEACAM5、PTX3、SPP1、PLXDC2与SPON2,AREG、CEACAM5、RET、LPL、KRT19与SPON2,PTX3、GDF15、RET、ADGRG2、BMP4与ADGRE1,TMPRSS15、COMP、PTX3、PGA4、POF1B与NPY,PTX3、POF1B、FCRL1、SOD3、PGA4与ITM2A,PTX3、POF1B、THBS4、FASLG、ITM2A与EXTL1,PTX3、POF1B、THBS4、EXTL1、PGA4与ITM2A,SPP1、COMP、LMNB2、FCRL1、LPL与LBP,PTX3、GDF15、THBS4、EXTL1、ADGRE1与ENPP6,SPP1、COMP、FCRL1、SOD3、CFP与LMNB2,PTX3、GDF15、THBS4、ADGRG2、ADGRE1与IL4R,SPP1、COMP、LMNB2、FCRL1、TNC与CLEC3B,ADGRE1、KRT19、LMNB2、COMP、PTX3与PGA4,PTX3、SPP1、ENPP6、COMP、TCL1A与ADGRE2,PTX3、GDF15、PLXDC2、THBS4、AGR3与TNC,SPP1、ITGA11、FCRL1、SOD3、LMNB2与PLXDC1,SPP1、COMP、LMNB2、FCRL1、PROK1与SOD3,TMPRSS15、PTX3、GDF15、COMP、ADGRE1与PGA4,SPP1、THBS4、LMNB2、ADGRE5、PROK1与BAG3,SPP1、COMP、LMNB2、FCRL1、ADGRE1与PTPRS,PTX3、ITGA11、POF1B、RET、SOD3与PGA4,SPP1、COMP、FCRL1、ADGRE5、LPL与LMNB2,SPP1、COMP、LMNB2、FCRL1、SOD3与CEACAM16,PTX3、GDF15、COMP、ADGRG2、ADGRE1与THBS4,PTX3、COMP、POF1B、FCRL1、PGA4与IL4R,PTX3、GDF15、THBS4、FASLG、TMPRSS15与ITM2A,TMPRSS15、PTX3、POF1B、THBS4、PGA4与CFP,PTX3、GDF15、THBS4、ADGRG2、BMP4与PROK1,PTX3、GDF15、COMP、EXTL1、PGA4与NOTCH1,ADGRE1、LMNB2、THBS4、TMPRSS15、GDF15与TNC,SPP1、COMP、LMNB2、SOD3、FCRL1与ASAH2,SPP1、COMP、FCRL1、ADGRE5、LMNB2与TNC,SPP1、PLXDC2、COMP、LMNB2、FCRL1与PLXDC1,SPP1、ADGRG2、FCRL1、SOD3、BAG3与LMNB2,GSN、TMPRSS15、PGA4、PTX3、POF1B与SOD3,TMPRSS15、PTX3、THBS4、FASLG、MMP12与ITM2A,TMPRSS15、PTX3、GDF15、THBS4、CCL7与ADGRE1,COMP、FCRL1、PTX3、GDF15、NOTCH1与PGA4,SPP1、THBS4、LMNB2、ADGRE5、CLEC3B与PROK1,PTX3、GDF15、THBS4、ADGRG2、PROK1与TCL1A,SPP1、COMP、LMNB2、FCRL1、CLEC3B与BAG3,TMPRSS15、SPP1、FCRL1、SOD3、PLXDC1与EDA2R,PTX3、GDF15、POF1B、THBS4、ADGRE5与TNC,TMPRSS15、PTX3、THBS4、FASLG、GDF15与AREG,SPP1、COMP、FCRL1、SOD3、TCL1A与LPL,PTX3、GDF15、THBS4、FASLG、ADGRE1与POF1B,TMPRSS15、PTX3、GDF15、THBS4、FASLG与TNC,PTX3、GDF15、THBS4、EXTL1、ITM2A与TNC,SPP1、LMNB2、FCRL1、SOD3、COMP与TMPRSS15,SPP1、LMNB2、SOD3、ADGRE5、FCRL1与NT5C1A,PTX3、GDF15、COMP、THBS4、ADGRE1与ITGA2,SPP1、PLXDC2、FCRL1、SOD3、ESM1与BAG3,TMPRSS15、PTX3、SPP1、THBS4、AREG与FASLG,或SPP1、COMP、LMNB2、FASLG、FCRL1与TCL1A；即上述84个6markers组合中的任意一种。Preferably, the 6 markers combination is: SPP1, PLXDC2, SOD3, IL4R, BAG3 and PROK1, AREG, CEACAM5, PTX3, CD48, CCL7 and IGFBP1, SPP1, PLXDC2, COMP, LMNB2, PROK1 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, PLXDC2 and BAG3, SPP1, COMP, LMNB2, SOD3, TCL1A and PRO K1, SPP1, LMNB2, FCRL1, SOD3, MEGF9 and PROK1, SPP1, LMNB2, SOD3, ADGRE5, TCL1A and PROK1, AREG, CEACAM5, PLXDC2, COMP, ADGRE2 and ADAMTS8, SPP1, COMP, FCRL1, SOD3, LMNB2 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, ADGRE1 and PLXDC1, SPP1 , COMP, LMNB2, FCRL1, PLXDC2 and PROK1, AREG, CEACAM5, SOD3, RET, CCL7 and MMP12, TMPRSS15, PTX3, COMP, POF1B, PGA4 and ITM2A, SPP1, PLXDC2, COMP, IL4R, TCL1A and PROK1, CRTAC1, SPP1, TCL1A, SOD3, LMNB2 and ADGRE2, PTX3, GDF15, POF1 B, THBS4, ADGRE1 and EXTL1, NOTCH1, COMP, GDF15, PTX3, PGA4 and CEACAM5, PTX3, POF1B, THBS4, ADGRE5, PGA4 and NPY, PTX3, LMNB2, SOD3, CNTN4, PGA4 and TCL1A, SPP1, LMNB2, FCRL1, SOD3, PLXDC1 and ITM2A, TMPRSS15, PTX3, GDF15, THBS4, AD GRE1 and IL4R, PTX3, COMP, HMCN2, POF1B, PGA4 and ADGRE1, SPP1, LMNB2, FCRL1, SOD3, ADGRE5 and C9, SPP1, PLXDC2, COMP, LMNB2, TCL1A and CLEC3B, SPP1, FCRL1, SOD3, ADGRE5, LMNB2 and CEACAM16, TMPRSS15, PTX3, GDF15, COMP, PGA4 and ITM2A ,PTX3,GDF15,THBS4,CLEC3B,ADGRE1 and TNC,GDF15,SPP1,PLXDC2,COMP,PROK1 and LMNB2,ADGRE1,GDF15,PTX3,THBS4,ADGRG2 and TNC,PTX3,GDF15,ENPP6,THBS4,ADGRE1 and AGR3,AREG,CEACAM5,PTX3,SPP1,PLXDC2 and SPON2,AREG,CEA CAM5, RET, LPL, KRT19 and SPON2, PTX3, GDF15, RET, ADGRG2, BMP4 and ADGRE1, TMPRSS15, COMP, PTX3, PGA4, POF1B and NPY, PTX3, POF1B, FCRL1, SOD3, PGA4 and ITM2A, PTX3, POF1B, THBS4, FASLG, ITM2A and EXTL1, PTX3, POF1B, THBS4, EXTL1, P GA4 and ITM2A, SPP1, COMP, LMNB2, FCRL1, LPL and LBP, PTX3, GDF15, THBS4, EXTL1, ADGRE1 and ENPP6, SPP1, COMP, FCRL1, SOD3, CFP and LMNB2, PTX3, GDF15, THBS4, ADGRG2, ADGRE1 and IL4R, SPP1, COMP, LMNB2, FCRL1, TNC and CLEC3B, ADGRE1, KRT 19, LMNB2, COMP, PTX3 and PGA4, PTX3, SPP1, ENPP6, COMP, TCL1A and ADGRE2, PTX3, GDF15, PLXDC2, THBS4, AGR3 and TNC, SPP1, ITGA11, FCRL1, SOD3, LMNB2 and PLXDC1, SPP1, COMP, LMNB2, FCRL1, PROK1 and SOD3, TMPRSS15, PTX3, GDF15, COMP, ADGRE1 and PGA4, SPP1, THBS4, LMNB2, ADGRE5, PROK1 and BAG3, SPP1, COMP, LMNB2, FCRL1, ADGRE1 and PTPRS, PTX3, ITGA11, POF1B, RET, SOD3 and PGA4, SPP1, COMP, FCRL1, ADGRE5, LPL and LMNB2, SPP1, COMP, LMNB2, FCRL1, SOD3 and CEACAM16, PT X3, GDF15, COMP, ADGRG2, ADGRE1 and THBS4, PTX3, COMP, POF1B, FCRL1, PGA4 and IL4R, PTX3, GDF15, THBS4, FASLG, TMPRSS15 and ITM2A, TMPRSS15, PTX3, POF1B, THBS4, PGA4 and CFP, PTX3, GDF15, THBS4, ADGRG2, BMP4 and PROK1, PTX3, GDF15, COMP, EXTL1, PGA4 and NOTCH1, ADGRE1, LMNB2, THBS4, TMPRSS15, GDF15 and TNC, SPP1, COMP, LMNB2, SOD3, FCRL1 and ASAH2, SPP1, COMP, FCRL1, ADGRE5, LMNB2 and TNC, SPP1, PLXDC2, COMP, LMNB2, FCRL1 and PLXDC1, SPP1, ADGRG2, FCRL1, SOD3, BAG3 and LMNB2, GSN, TMPRSS15, PGA4, PTX3, POF1B and SOD3, TMPRSS15, PTX3, THBS4, FASLG, MMP12 and ITM2A, TMPRSS15, PTX3, GDF15, THBS4, CCL7 and ADGRE1, COMP, FCRL1, PTX3, GDF15, NOTCH1 and PGA4, SPP1, THBS4, LMNB2, ADGRE5, CLEC3B and PROK1, PTX3, GDF15, THBS4, ADGRG2, PROK1 and TCL1A, SPP1, COMP, LMNB2, FCRL1, CLEC3B and BAG3, TMPRSS15, SPP1, FCRL1, SOD3, PLXDC1 and EDA2R, PTX3, GDF15, POF1B, THBS4, ADGRE5 and TNC, TMPRSS15, PTX3, THBS4, FASLG, GDF15 and AREG ,SPP1,COMP,FCRL1,SOD3,TCL1A and LPL,PTX3,GDF15,THBS4,FASLG,ADGRE1 and POF1B,TMPRSS15,PTX3,GDF15,THBS4,FASLG and TNC,PTX3,GDF15,THBS4,EXTL1,ITM2A and TNC,SPP1,LMNB2,FCRL1,SOD3,COMP and TMPRSS15,SPP1,LMNB2,S OD3, ADGRE5, FCRL1 and NT5C1A, PTX3, GDF15, COMP, THBS4, ADGRE1 and ITGA2, SPP1, PLXDC2, FCRL1, SOD3, ESM1 and BAG3, TMPRSS15, PTX3, SPP1, THBS4, AREG and FASLG, or SPP1, COMP, LMNB2, FASLG, FCRL1 and TCL1A; that is, any one of the above 84 6-markers combinations.
优选地，所述6markers组合为所述E中的任意六种。Preferably, the 6 markers combination is any six of the E.
优选地，所述6markers组合为：CEACAM5、COMP、PTX3、TNC、NOTCH1与GDF15，CEACAM5、COMP、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC与GDF15，CEACAM5、COMP、PTX3、NOTCH1、SERPINA1与GDF15，COMP、PTX3、AREG、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与GDF15，COMP、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与EDA2R，，TMPRSS15、COMP、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、TNC与GDF15，COMP、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1与GDF15，COMP、PTX3、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、PTX3、AREG、NOTCH1与GDF15，COMP、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1与GDF15，COMP、PTX3、AREG、TNC、NOTCH1与GDF15，COMP、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、TNC、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG与EDA2R，CEACAM5、COMP、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG与GDF15，TMPRSS15、COMP、FCRL1、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG与EDA2R，CEACAM5、COMP、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG与EDA2R，CEACAM5、COMP、PTX3、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC与EDA2R，TMPRSS15、COMP、PTX3、TNC、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG与GDF15，TMPRSS15、COMP、FCRL1、TNC、SERPINA1与EDA2R，COMP、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、SERPINA1与EDA2R，TMPRSS15、COMP、PTX3、AREG、NOTCH1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC与EDA2R，COMP、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、AREG、TNC与GDF15，COMP、FCRL1、PTX3、AREG、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、TNC、SERPINA1与GDF15，COMP、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、NOTCH1与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC与EDA2R，CEACAM5、COMP、FCRL1、AREG、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1与GDF15，TMPRSS15、COMP、AREG、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG与GDF15，CEACAM5、COMP、PTX3、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC与GDF15，CEACAM5、COMP、AREG、TNC、NOTCH1与GDF15，COMP、FCRL1、PTX3、AREG、GDF15与EDA2R，TMPRSS15、PTX3、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、TNC、SERPINA1、GDF15与EDA2R，COMP、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、PTX3、AREG、TNC与GDF15，TMPRSS15、COMP、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、TNC、NOTCH1与EDA2R，TMPRSS15、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC与GDF15，TMPRSS15、COMP、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、SERPINA1与GDF15，TMPRSS15、PTX3、AREG、TNC、NOTCH1与GDF15，CEACAM5、COMP、FCRL1、AREG、SERPINA1与EDA2R，CEACAM5、COMP、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、NOTCH1与GDF15，CEACAM5、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG与GDF15，CEACAM5、COMP、FCRL1、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、GDF15与EDA2R，CEACAM5、COMP、PTX3、NOTCH1、SERPINA1与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、TNC、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、NOTCH1、GDF15与EDA2R，CEACAM5、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、NOTCH1与EDA2R，TMPRSS15、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、AREG、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、TNC、SERPINA1与GDF15，COMP、FCRL1、PTX3、TNC、GDF15与EDA2R，COMP、FCRL1、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、TNC与EDA2R，TMPRSS15、CEACAM5、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、PTX3、TNC、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、AREG、NOTCH1、GDF15与EDA2R，CEACAM5、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC与EDA2R，TMPRSS15、COMP、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1与GDF15，COMP、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1与GDF15，TMPRSS15、CEACAM5、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1与GDF15，COMP、PTX3、AREG、TNC、GDF15与EDA2R，COMP、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、SERPINA1与GDF15，TMPRSS15、COMP、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、SERPINA1与EDA2R，COMP、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、GDF15与EDA2R，CEACAM5、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、SERPINA1与EDA2R，COMP、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、SERPINA1与GDF15，CEACAM5、COMP、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、GDF15与EDA2R，TMPRSS15、COMP、PTX3、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、TNC、NOTCH1、SERPINA1与GDF15，FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、AREG、SERPINA1与GDF15，TMPRSS15、COMP、AREG、TNC、SERPINA1与GDF15，TMPRSS15、PTX3、AREG、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1与GDF15，TMPRSS15、FCRL1、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1与GDF15，CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、GDF15与EDA2R，COMP、FCRL1、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、SERPINA1与GDF15，TMPRSS15、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1与EDA2R，COMP、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、PTX3、AREG、TNC与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、PTX3、AREG、TNC、GDF15与EDA2R，FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、SERPINA1、GDF15与EDA2R，COMP、PTX3、AREG、TNC、NOTCH1与EDA2R，COMP、FCRL1、PTX3、AREG、SERPINA1与GDF15，COMP、FCRL1、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、PTX3、TNC、SERPINA1与EDA2R，COMP、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、GDF15与EDA2R，CEACAM5、COMP、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、AREG、NOTCH1、GDF15与EDA2R，COMP、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、SERPINA1与GDF15，PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、FCRL1、AREG、TNC、NOTCH1与GDF15，FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、TNC、SERPINA1与GDF15，TMPRSS15、COMP、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1与EDA2R，CEACAM5、COMP、AREG、NOTCH1、SERPINA1与EDA2R，COMP、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG与EDA2R，TMPRSS15、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与TNC，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC与NOTCH1，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与AREG，FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、SERPINA1、GDF15与EDA2R，PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG与TNC，TMPRSS15、FCRL1、AREG、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC与GDF15，CEACAM5、COMP、AREG、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG与TNC，TMPRSS15、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、PTX3、AREG、NOTCH1、GDF15与EDA2R，FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC与GDF15，TMPRSS15、CEACAM5、FCRL1、TNC、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、SERPINA1与EDA2R，CEACAM5、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、TNC与EDA2R，TMPRSS15、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、GDF15与EDA2R，CEACAM5、COMP、FCRL1、TNC、GDF15与EDA2R，PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC与SERPINA1，CEACAM5、AREG、TNC、NOTCH1、GDF15与EDA2R，COMP、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC与GDF15，CEACAM5、COMP、AREG、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、FCRL1、AREG、TNC与EDA2R，CEACAM5、COMP、FCRL1、AREG、SERPINA1与GDF15，CEACAM5、COMP、AREG、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、AREG、TNC、NOTCH1与EDA2R，COMP、FCRL1、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、AREG、TNC、SERPINA1与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1与EDA2R，TMPRSS15、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC与SERPINA1，CEACAM5、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、PTX3、AREG、TNC、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1与GDF15，CEACAM5、COMP、AREG、SERPINA1、GDF15与EDA2R，COMP、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1与EDA2R，TMPRSS15、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG与NOTCH1，TMPRSS15、FCRL1、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG与GDF15，COMP、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC与NOTCH1，FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG与TNC，CEACAM5、COMP、FCRL1、PTX3、AREG与NOTCH1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC与NOTCH1，TMPRSS15、FCRL1、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG与TNC，TMPRSS15、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC与NOTCH1，CEACAM5、FCRL1、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、TNC、SERPINA1、GDF15与EDA2R，FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC与GDF15，TMPRSS15、CEACAM5、FCRL1、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG与TNC，CEACAM5、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC与NOTCH1，TMPRSS15、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC与NOTCH1，CEACAM5、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG与NOTCH1，TMPRSS15、CEACAM5、COMP、FCRL1、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、PTX3、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与NOTCH1，TMPRSS15、COMP、FCRL1、PTX3、TNC与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC与GDF15，CEACAM5、COMP、PTX3、AREG、TNC与NOTCH1，TMPRSS15、COMP、FCRL1、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、PTX3、NOTCH1与SERPINA1，CEACAM5、COMP、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC与NOTCH1，FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、AREG、TNC、SERPINA1与GDF15，FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG与SERPINA1，CEACAM5、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、AREG、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1与SERPINA1，COMP、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3与SERPINA1，TMPRSS15、COMP、PTX3、AREG、TNC与NOTCH1，CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1，CEACAM5、COMP、FCRL1、PTX3、TNC与SERPINA1，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、SERPINA1与EDA2R，CEACAM5、FCRL1、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、COMP、FCRL1、AREG、TNC与SERPINA1，TMPRSS15、COMP、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1与SERPINA1，TMPRSS15、COMP、PTX3、AREG、TNC与SERPINA1，CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1与SERPINA1，TMPRSS15、FCRL1、PTX3、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、AREG、SERPINA1与GDF15，FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC与SERPINA1，AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG与SERPINA1，COMP、FCRL1、PTX3、AREG、TNC与NOTCH1，TMPRSS15、COMP、FCRL1、TNC、NOTCH1与SERPINA1，COMP、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、TNC与SERPINA1，TMPRSS15、CEACAM5、COMP、FCRL1、AREG与NOTCH1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG与NOTCH1，CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、FCRL1、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1与SERPINA1，COMP、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、PTX3、AREG与SERPINA1，CEACAM5、COMP、FCRL1、AREG、NOTCH1与SERPINA1，COMP、FCRL1、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、TNC、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、TNC与NOTCH1，TMPRSS15、FCRL1、PTX3、AREG、TNC与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1与SERPINA1，COMP、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，COMP、FCRL1、PTX3、AREG、TNC与SERPINA1，CEACAM5、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1与SERPINA1，TMPRSS15、FCRL1、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、TNC与GDF15，TMPRSS15、COMP、PTX3、TNC、NOTCH1与SERPINA1，CEACAM5、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、PTX3、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、AREG、TNC、NOTCH1与SERPINA1，PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、SERPINA1与GDF15，FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、TNC、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC与EDA2R，CEACAM5、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、PTX3、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、AREG、TNC、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC与SERPINA1，CEACAM5、PTX3、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、TNC、GDF15与EDA2R，CEACAM5、PTX3、AREG、TNC、SERPINA1与EDA2R，FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、SERPINA1、GDF15与EDA2R，或CEACAM5、AREG、TNC、SERPINA1、GDF15与EDA2R。Preferably, the 6 markers combination is: CEACAM5, COMP, PTX3, TNC, NOTCH1 and GDF15, CEACAM5, COMP, PTX3, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1 and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, TNC and GDF15, CEACAM5, COMP, PTX3, NOTCH1, SERPINA1 and GDF15, COMP, PTX3, AREG, NOTCH1, GDF15 and EDA2R, COMP, FCRL1, PTX3, AREG, NOTCH1 and GDF15, TMPRSS15, COMP, PTX3, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, and GDF15, COMP, FCRL1, PTX3, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, and EDA2R, , TMPRSS15, COMP, PTX3, TNC, NOTCH1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, TNC, and GDF15, COMP, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM 5. PTX3, TNC, NOTCH1, and GDF15, COMP, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, CEACAM5, COMP, PTX3, AREG, NOTCH1, and GDF15, COMP, PTX3, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, PTX3, AREG, TNC, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, AREG, GDF15, and EDA2R , COMP, FCRL1, PTX3, TNC, NOTCH1, AND GDF15, TMPRSS15, CEACAM5, COMP, PTX3, TNC, AND EDA2R, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, AND GDF15, COMP, PTX3, AREG, TNC, NOTCH1, AND GDF15, COMP, FCRL1, NOTCH1, SERPINA1, GDF15, AND EDA2R, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, COMP, FCRL1, AREG, TNC, NOTCH1, AND GDF15, TMPRSS15, COMP, FCRL1, TNC, G DF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, NOTCH1 and GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG and EDA2R, CEACAM5, COMP, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG and GDF15, TMPRSS15, COMP, FCRL1, TNC, NOTCH1 and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG and EDA2R, CEACAM5, COMP, TNC, NOTCH1, SERPINA1 and GDF15, CEACAM 5.COMP, FCRL1, PTX3, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, SERPINA1 and GDF15, CEACAM5, COMP, FCRL1, PTX3, AREG and EDA2R, CEACAM5, COMP, PTX3, TNC, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1 and GDF15, TMPRSS15, COMP, FCRL1, PTX3 、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC与EDA2R，TMPRSS15、COMP、PTX3、TNC、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC和GDF15，TMPRSS15、CEACAM5、COMP、PTX3、SERPINA1与GDF15，TMPRS S15, FCRL1, PTX3, TNC, NOTCH1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, and GDF15, TMPRSS15, COMP, FCRL1, TNC, SERPINA1, and EDA2R, COMP, FCRL1, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, SERPINA1, and EDA2R, TMPRSS15, COMP, PTX3, AREG, NOTCH1, and EDA2R, CEACAM5, COMP , PTX3, AREG, TNC, AND GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, AND EDA2R, COMP, PTX3, AREG, NOTCH1, SERPINA1, AND GDF15, TMPRSS15, CEACAM5, COMP, AREG, TNC, AND GDF15, COMP, FCRL1, PTX3, AREG, NOTCH1, AND EDA2R, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1, AND GDF15, TMPRSS15, COMP, FCRL1, NOTCH1, SERPINA1, AND GDF15, COMP, FCRL1, PTX3, NOTCH1, SER PINA1 and EDA2R, TMPRSS15, FCRL1, PTX3, NOTCH1, GDF15 and EDA2R, COMP, FCRL1, PTX3, TNC, SERPINA1 and GDF15, TMPRSS15, COMP, FCRL1, AREG, SERPINA1 and EDA2R, TMPRSS15, COMP, FCRL1, TNC, SERPINA1 and GDF15, COMP, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, PTX3, AREG, NOTCH1 and EDA2R, TMPRSS15, COMP, AREG, TNC, NOTCH1 and EDA2R, CE ACAM5, COMP, FCRL1, PTX3, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, and EDA2R, CEACAM5, COMP, FCRL1, AREG, NOTCH1, and GDF15, TMPRSS15, COMP, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, and GDF15, TMPRSS15, COMP, AREG, NOTCH1, and GDF15, CEACAM5, C OMP, FCRL1, PTX3, AREG, and GDF15, CEACAM5, COMP, PTX3, AREG, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, NOTCH1, and GDF15, TMPRSS15, COMP, PTX3, AREG, TNC, and GDF15, CEACAM5, COMP, AREG, TNC, NOTCH1, and GDF15, COMP, FCRL1, PTX3, AREG, GDF15, and EDA2R, TMPRSS15, PTX3, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, PTX3, TNC, NOTCH1, SERPINA1, and GDF1 5,TMPRSS15,COMP,TNC,SERPINA1,GDF15,AND EDA2R,COMP,FCRL1,AREG,NOTCH1,SERPINA1,AND GDF15,COMP,FCRL1,PTX3,AREG,TNC,AND GDF15,TMPRSS15,COMP,PTX3,AREG,NOTCH1,AND GDF15,TMPRSS15,COMP,FCRL1,TNC,NOTCH1,AND EDA2R,TMPRSS15,FCRL1,PTX3,NOTCH1,SERPINA1,AND GDF15,CEACAM5,COMP,PTX3,TNC,NOTCH1,AND EDA2R,TMPRSS15,COMP,F CRL1, AREG, TNC, and GDF15, TMPRSS15, COMP, PTX3, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, SERPINA1, and GDF15, TMPRSS15, PTX3, AREG, TNC, NOTCH1, and GDF15, CEACAM5, COMP, FCRL1, AREG, SERPINA1, and EDA2R, CEACAM5, COMP, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, TNC, NOTCH1, GD F15 and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, NOTCH1 and GDF15, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1 and GDF15, TMPRSS15, PTX3, AREG, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, PTX3, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, NOTCH1 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1 and GDF15, CEACAM5, PTX3, AREG, TNC, NOTCH1 and GDF15, TMPRSS15, COMP, FCRL1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, and GDF15, CEACAM5, COMP, FCRL1, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, GDF15, and EDA2R, CEACAM5, COMP, PTX3, NOTCH1, SERPINA1, and EDA2R, COMP, FCRL1, PTX3, TNC, NOTCH1, and EDA2R, CEACAM5, COMP, FCRL1, TNC, SERPINA1, and EDA2R, TMPRSS1 5. COMP, FCRL1, NOTCH1, GDF15, and EDA2R, CEACAM5, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, NOTCH1, and EDA2R, TMPRSS15, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, AREG, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, PTX3, TNC, SERPINA1, and GDF15, COMP, FCRL1, PTX3, TNC, GDF15, and EDA2R, COMP, FCRL1, TNC, NOTCH 1. GDF15 and EDA2R, COMP, FCRL1, PTX3, AREG, TNC and EDA2R, TMPRSS15, CEACAM5, TNC, NOTCH1, SERPINA1 and GDF15, TMPRSS15, PTX3, TNC, NOTCH1, SERPINA1 and GDF15, COMP, FCRL1, AREG, NOTCH1, GDF15 and EDA2R, CEACAM5, PTX3, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, AREG, TNC, SERPINA1 and EDA2R, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1 and EDA2 R, CEACAM5, COMP, FCRL1, PTX3, TNC, and EDA2R, TMPRSS15, COMP, PTX3, AREG, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, AREG, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, TNC, NOTCH1, and GDF15, COMP, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, NOTCH1, and GDF15, TMPRSS15, CEACAM5, PTX3, NOTCH1, and GDF15, and EDA2R, TM PRSS15, COMP, AREG, TNC, NOTCH1, and GDF15, COMP, PTX3, AREG, TNC, GDF15, and EDA2R, COMP, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, SERPINA1, and GDF15, TMPRSS15, COMP, NOTCH1, SERPINA1, GDF15, and EDA2R, COMP, FCRL1, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, SERPINA1, and EDA2R, COMP, PTX3, AREG 、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，CEACAM5、COMP 、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、GDF15与EDA2R，CEACAM5、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、SERPINA1与EDA2R，COMP、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、SERPINA1与GDF15，CEACAM5、COMP、PTX 3.SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, PTX3, TNC, GDF15 and EDA2R, TMPRSS15, COMP, PTX3, NOTCH1, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, NOTCH1 and GDF15, CEACAM5, FCRL1, PTX3, NOTCH1, SERPINA1 and GDF15, TMPRSS15, COMP, PTX3, TNC, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, NOTCH1 and EDA2R, TMPRSS15, COMP, TNC, NOTCH 1.SERPINA1 and GDF15, FCRL1, PTX3, AREG, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, AREG, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, NOTCH1 and GDF15, TMPRSS15, CEACAM5, COMP, AREG, SERPINA1 and GDF15, TMPRSS15, COMP, AREG, TNC, SERPINA1 and GDF15, TMPRSS15, PTX3, AREG, NOTCH1, SERPINA1 and GDF15, COMP, FCRL1, AREG, NOTCH1, SER PINA1 and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1 and GDF15, TMPRSS15, FCRL1, AREG, TNC, GDF15 and EDA2R, CEACAM5, COMP, PTX3, AREG, SERPINA1 and GDF15, TMPRSS15, PTX3, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, AREG, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1 and GDF15, CEACAM5, FCRL1, TNC, NOTCH1, SERPIN A1 and GDF15, TMPRSS15, FCRL1, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, AREG, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, GDF15 and EDA2R, COMP, FCRL1, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, NOTCH1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, SERPINA1 and GDF15, TMPRSS15, AREG, TNC, NOTC H1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1 and EDA2R, COMP, AREG, TNC, NOTCH1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, TNC and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, NOTCH1 and EDA2R, TMPRSS15, PTX3, AREG, TNC, GDF15 and EDA2R, FCRL1, PTX3, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1 and EDA2R , TMPRSS15, CEACAM5, COMP, SERPINA1, GDF15, and EDA2R, COMP, PTX3, AREG, TNC, NOTCH1, and EDA2R, COMP, FCRL1, PTX3, AREG, SERPINA1, and GDF15, COMP, FCRL1, AREG, TNC, GDF15, and EDA2R, CEACAM5, COMP, PTX3, TNC, SERPINA1, and EDA2R, COMP, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, GDF1 5 and EDA2R, CEACAM5, COMP, AREG, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, PTX3, NOTCH1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, AREG, NOTCH1, GDF15 and EDA2R, COMP, PTX3, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS15, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, COMP, FCRL1, AREG, TNC, SERPINA1 and GDF15, PTX3, AREG, TNC, NOTCH1, SERPINA1 and GDF1 5,TMPRSS15,FCRL1,TNC,NOTCH1,GDF15,AND EDA2R,CEACAM5,COMP,PTX3,AREG,SERPINA1,AND EDA2R,TMPRSS15,FCRL1,AREG,TNC,NOTCH1,AND GDF15,FCRL1,PTX3,TNC,NOTCH1,SERPINA1,AND GDF15,CEACAM5,COMP,FCRL1,TNC,SERPINA1,AND GDF15,TMPRSS15,COMP,TNC,NOTCH1,SERPINA1,AND EDA2R,TMPRSS15,FCRL1,PTX3,AREG,NOTCH1,AND EDA2R,CEACAM5, COMP, AREG, NOTCH1, SERPINA1, and EDA2R, COMP, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, GDF15, and EDA2R, COMP, FCRL1, AREG, TNC, NOTCH1, and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, and EDA2R, TMPRSS15, FCRL1, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, FCRL1, PTX3, TNC , SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, and TNC, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, and NOTCH1, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, and AREG, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, SERPINA1, GDF15, and EDA2R, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG and TNC, TMPRSS15, FCRL1, AREG, NOTCH1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC and GDF15, CEACAM5, COMP, AREG, NOTCH1, SERPINA1 and GDF15, CEACAM5, COMP, FCRL1, TNC, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG and TNC, TMPRSS1 5, PTX3, AREG, TNC, NOTCH1, and EDA2R, CEACAM5, PTX3, AREG, NOTCH1, GDF15, and EDA2R, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, and GDF15, TMPRSS15, CEACAM5, FCRL1, TNC, GDF15, and EDA2R, CEACAM5, FCRL1, PTX3, NOTCH1, GDF15, and EDA2R, COMP, FCRL1, PTX3, AREG, SERPINA1, and EDA2R, CEACAM5, FCRL1, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, FCRL1, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1 and EDA2R, TMPRSS15, FCRL1, AREG, NOTCH1, SERPINA1 and GDF15, TMPRSS15, FCRL1, PTX3, AREG, TNC and EDA2R, TMPRSS15, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, PTX3, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1 、AREG、GDF15与EDA2R，CEACAM5、COMP、FCRL1、TNC、GDF15与EDA2R，PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC和SERPINA1，CEACAM5、AREG、TNC、GDF15与EDA2R，COMP、AREG、TNC、NOTCH1、SERPINA1和EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC和GDF15，CEACAM5、COMP、AREG、TNC、GDF15与EDA2R，TMPR SS15, CEACAM5, PTX3, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, AREG, TNC, NOTCH1, and GDF15, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, and EDA2R, CEACAM5, COMP, FCRL1, AREG, SERPINA1, and GDF15, CEACAM5, COMP, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, and EDA2R, COMP, FCRL 1, TNC, SERPINA1, GDF15 and EDA2R, TMPRSS15, FCRL1, AREG, TNC, SERPINA1 and EDA2R, CEACAM5, COMP, AREG, TNC, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, GDF15 and EDA2R, COMP, FCRL1, AREG, TNC, SERPINA1 and EDA2R, TMPRSS15, PTX3, TNC, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, FCRL1 , PTX3, NOTCH1, AND EDA2R, TMPRSS15, PTX3, AREG, NOTCH1, SERPINA1, AND EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, AND SERPINA1, CEACAM5, TNC, NOTCH1, SERPINA1, GDF15, AND EDA2R, TMPRSS15, PTX3, AREG, TNC, SERPINA1, AND EDA2R, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, AND EDA2R, TMPRSS15, CEACAM5, TNC, NOTCH1, SERPINA1, AND EDA2R, CEACAM5, AREG, TNC, NO TCH1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, TNC and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1 and GDF15, CEACAM5, COMP, AREG, SERPINA1, GDF15 and EDA2R, COMP, PTX3, AREG, TNC, SERPINA1 and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, SERPINA1 and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC and EDA2R, TMPRSS15, CEACAM5, FCR L1, TNC, NOTCH1, and EDA2R, TMPRSS15, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, and NOTCH1, TMPRSS15, FCRL1, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, and GDF15, COMP, PTX3, ARE G, TNC, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC and NOTCH1, FCRL1, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG and TNC, CEACAM5, COMP, FCRL1, PTX3, AREG and NOTCH1, TMPRSS15, CEACAM5, FCRL1, AREG , TNC and NOTCH1, TMPRSS15, FCRL1, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, SERPINA1 and EDA2R, CEACAM5, COMP, FCRL1, TNC, NOTCH1 and SERPINA1, TMPRSS15, CEACAM5, COMP, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG and TNC, TMPRSS15, FCRL1, AREG, NOTCH1, SERPINA1 and EDA2R, CEACAM5, PTX3, TNC, NOTC H1,SERPINA1 and EDA2R,CEACAM5,FCRL1,AREG,NOTCH1,SERPINA1 and GDF15,TMPRSS15,PTX3,TNC,SERPINA1,GDF15 and EDA2R,TMPRSS15,COMP,FCRL1,PTX3,TNC and NOTCH1,CEACAM5,FCRL1,TNC,NOTCH1,GDF15 and EDA2R,CEACAM5,AREG,NOTCH1,SERPINA1,GDF15 and EDA2R,CEACAM5,COMP,TNC,SERPINA1,GDF15 and EDA2R,FCRL1,AREG,TNC,NOTCH1,SERP INA1 and GDF15, TMPRSS15, FCRL1, TNC, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, PTX3, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, TNC and GDF15, TMPRSS15, CEACAM5, FCRL1, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, SERPINA1 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, SERPINA1 and EDA2R, CEACAM5, FCRL1, PTX3, NOTCH1,SERPINA1,AND EDA2R,TMPRSS15,CEACAM5,FCRL1,NOTCH1,SERPINA1AND GDF15,TMPRSS15,CEACAM5,FCRL1,PTX3,AREG,AND TNC,CEACAM5,AREG,TNC,NOTCH1,SERPINA1AND EDA2R,TMPRSS15,CEACAM5,TNC,SERPINA1,GDF15,TMPRSS15,FCRL1,PTX3,AREG,SERPINA1AND EDA2R,TMPRSS15,CEACAM5,FCRL1,AREG,NOTCH1AND EDA2R,TMPRSS15,C EACAM5, COMP, PTX3, AREG, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, and NOTCH1, TMPRSS15, PTX3, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, and NOTCH1, CEACAM5, PTX3, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, COMP , FCRL1, PTX3, AREG, and NOTCH1, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, PTX3, TNC, NOTCH1, and SERPINA1, CEACAM5, COMP, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, COMP, PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, PTX3, AREG, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5 M5, COMP, FCRL1, PTX3, and NOTCH1, TMPRSS15, COMP, FCRL1, PTX3, TNC, and SERPINA1, TMPRSS15, CEACAM5, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, AREG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, PTX3, TNC, SERPINA1, and EDA2R, TMPRSS15, COMP, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, C EACAM5, FCRL1, AREG, TNC, and GDF15, CEACAM5, COMP, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, COMP, FCRL1, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1, and SERPINA1, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, and SERPINA1, CEACAM5, COMP, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, PTX3, SERPINA1, GDF15, and EDA2R, TMPRSS15, F CRL1, PTX3, NOTCH1, SERPINA1, and EDA2R, FCRL1, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, and NOTCH1, FCRL1, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, FCRL1, AREG, TNC, SERPINA1, and GDF15, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1 , PTX3, AREG, and SERPINA1, CEACAM5, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, AREG, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, TNC, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, COMP, TNC, NOTCH1, AND SERPINA1, COMP, AREG, TNC, SERPINA1, GDF15, AND EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, AND SERPINA1, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AND SERPINA1, TMPRSS15, COMP, PTX3, AREG, TNC, AND NOTCH1, CEACAM5, COMP, PTX3, AREG, TNC, SERPINA1, CEACAM5, COMP, FCRL1, PTX3, TNC, AND SERPINA1, TMPRSS15, CEACAM5, PTX3, T NC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, PTX3, AREG, SERPINA1, and EDA2R, CEACAM5, FCRL1, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, COMP, FCRL1, AREG, TNC, and SERPINA1, TMPRSS15, COMP, PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5 , PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, and SERPINA1, TMPRSS15, COMP, PTX3, AREG, TNC, and SERPINA1, CEACAM5, FCRL1, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, and SERPINA1, TMPRSS15, FCRL1, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, AREG, SERPINA1, and GDF15, FCRL1, PT X3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC与SERPINA1，AREG、TNC、NOTCH1、SERPINA1，GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、SERPINA1，COMP、FCRL1、PTX3、AREG、TNC和NOTCH1，TMPRSS15、COMP、FCRL1、TNC、NOTCH1和SERPINA1，COMP、PTX3、AREG、TNC、NOTCH1和SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3， TNC and SERPINA1,TMPRSS15,CEACAM5,PTX3,AREG,TNC and SERPINA1,TMPRSS15,CEACAM5,COMP,FCRL1,AREG and NOTCH1,TMPRSS15,CEACAM5,FCRL1,PTX3,AREG and NOTCH1,CEACAM5,FCRL1,AREG,NOTCH1,SERPINA1 and EDA2R,FCRL1,PTX3,AREG,NOTCH1,SERPINA1 and EDA2R,CEACAM5,FCRL1,AREG,TNC,NOTCH1 and EDA2R,TMPRSS15,CEACAM5,FCRL1,TNC,N OTCH1 and SERPINA1, COMP, FCRL1, PTX3, AREG, NOTCH1 and SERPINA1, CEACAM5, COMP, FCRL1, PTX3, AREG, and SERPINA1, CEACAM5, COMP, FCRL1, AREG, NOTCH1 and SERPINA1, COMP, FCRL1, AREG, TNC, NOTCH1 and SERPINA1, CEACAM5, FCRL1, PTX3, TNC, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, NOTCH1 and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, TNC and NOTCH1, TMPRSS15, FCRL1, PTX3, AREG, TNC, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, NOTCH1, and SERPINA1, COMP, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, COMP, FCRL1, PTX3, AREG, TNC, and SERPINA1, CEACAM5, FCRL1, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, SERPINA1, GDF15, and EDA2R, TMPRS S15, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1, and SERPINA1, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, TNC, and GDF15, TMPRSS15, COMP, PTX3, TNC, NOTCH1, and SERPINA1, CEACAM5 , PTX3, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, PTX3, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, CEACAM5, FCRL1, AREG, TNC, NOTCH1, and SERPINA1, PTX3, AREG, TNC, NOTCH1, and SERPINA1, FCRL1, PTX3, AREG, TNC, SERPINA1, and EDA2R, GDF15, FCRL1, PTX3, TNC, S ERPINA1, GDF15 and EDA2R, FCRL1, AREG, TNC, NOTCH1, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, NOTCH1 and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, SERPINA1 and GDF15, CEACAM5, FCRL1, PTX3, TNC, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC and EDA2R, CEACA M5, PTX3, AREG, TNC, GDF15 and EDA2R, CEACAM5, PTX3, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, PTX3, AREG, TNC, SERPINA1 and GDF15, CEACAM5, FCRL1, AREG, TNC, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, SERPINA1 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1, CEACAM5, PTX3, AREG, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, AREG, TNC, SERPINA1 and GDF15, CEACAM5, FCRL1, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, AREG, TNC, GDF15 and EDA2R, CEACAM5, PTX3, AREG, TNC, SERPINA1 and EDA2R, FCRL1, AREG, TNC, SERPINA1, GDF15 and EDA2R, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, AREG, SERPINA1, GDF15 and EDA2R, or CEACAM5, AREG, TNC, SERPINA1, GDF15 and EDA2R.
优选地，所述A包含7markers组合，所述7markers组合为所述B中的任意七种。Preferably, the A comprises a combination of 7 markers, and the combination of 7 markers is any seven of the combinations in B.
优选地，所述7markers组合为e1)和e2):Preferably, the 7 markers are combined into e1) and e2):
e1)所述6markers组合(优选上述84个6markers组合中的任一种)；e1) the 6-markers combination (preferably any one of the above 84 6-markers combinations);
e2)所述B中的任意一种；e2) any one of the above B;
所述e2)不同于e1)中所述6markers组合中的任意一个marker。The e2) is different from any marker in the combination of 6 markers in e1).
优选地，所述7markers组合为：SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与ADGRG2，SPP1、COMP、LMNB2、SOD3、TCL1A、PROK1与ADGRG2，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与ADGRG2，SPP1、LMNB2、FCRL1、SOD3、PLXDC2、BAG3与PROK1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A与SOD3，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与POF1B，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与POF1B，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与THBS4，PTX3、POF1B、FCRL1、SOD3、PGA4、ITM2A与PCDH7，PTX3、GDF15、ENPP6、THBS4、ADGRE1、AGR3与TNC，SPP1、PLXDC2、COMP、LMNB2、PROK1、BAG3与AREG，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与SOD3，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与BAG3，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与FCER2，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与BAG3，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与CNTN4，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与ITGA11，SPP1、PLXDC2、COMP、LMNB2、PROK1、BAG3与ITM2A，SPP1、LMNB2、SOD3、ADGRE5、TCL1A、ADGRG2与PROK1，SPP1、PLXDC2、COMP、LMNB2、TCL1A、SOD3与PROK1，SPP1、PLXDC2、SOD3、IL4R、BAG3、PROK1与LMNB2，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A与PCDH7，SPP1、COMP、LMNB2、SOD3、ADGRE1、FCRL1与TCL1A，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与SOD3，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与IL6，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与IL4R，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与FGF21，SPP1、COMP、LMNB2、SOD3、FCRL1、TCL1A与LPL，SPP1、PLXDC2、COMP、LMNB2、TCL1A、IL4R与PROK1，PTX3、POF1B、FCRL1、SOD3、PGA4、ITM2A与EXTL1，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与IL4R，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A与PTPRS，SPP1、LMNB2、FCRL1、SOD3、PLXDC1、CDH23与ADGRE5，SPP1、COMP、FCRL1、SOD3、TCL1A、LMNB2与ADGRE1，SPP1、PLXDC2、COMP、LMNB2、TCL1A、IGFBP1与PROK1，SPP1、PLXDC2、COMP、LMNB2、PROK1、TCL1A与CNTN1，PTX3、POF1B、FCRL1、SOD3、PGA4、ITM2A与PLXDC1，SPP1、PLXDC2、COMP、LMNB2、TCL1A、CLEC3B与PROK1，SPP1、PLXDC2、COMP、LMNB2、TCL1A、PROK1与PTPRS，或PTX3、POF1B、THBS4、EXTL1、PGA4、SOD3与ITM2A；即上述40个7markers组合中的任意一种。Preferably, the 7 markers combination is: SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and ADGRG2, SPP1, COMP, LMNB2, SOD3, TCL1A, PROK1 and ADGRG2, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and ADGRG2, SPP1, LMNB2, FCRL1, SOD3, PLXDC2, BAG3 and PROK1, PTX3, POF1B, THBS4, EXTL1, P GA4, ITM2A and SOD3, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and POF1B, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and POF1B, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and THBS4, PTX3, POF1B, FCRL1, SOD3, PGA4, ITM2A and PCDH7, PTX3, GDF15, ENPP6, THBS4, ADGRE1, AGR3 and TNC, SPP1, PLXDC2, COMP, LMNB2, PROK1, BAG3 and AREG, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and SOD3, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and BAG3, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and FCER2, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and BAG 3, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and CNTN4, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and ITGA11, SPP1, PLXDC2, COMP, LMNB2, PROK1, BAG3 and ITM2A, SPP1, LMNB2, SOD3, ADGRE5, TCL1A, ADGRG2 and PROK1, SPP1, PLXDC2, COMP, LMNB2, TCL1A, SOD3 and PROK1, SPP1, PLXDC2, SOD3, IL4R, BAG3, PROK1 and LMNB2, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A and PCDH7, SPP1, COMP, LMNB2, SOD3, ADGRE1, FCRL1 and TCL1A, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and SOD3, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and IL6, SPP1, PLX DC2, COMP, LMNB2, PROK1, TCL1A and IL4R, SPP1, PLXDC2, COMP, LMNB2, PROK1, TCL1A and FGF21, SPP1, COMP, LMNB2, SOD3, FCRL1, TCL1A and LPL, SPP1, PLXDC2, COMP, LMNB2, TCL1A, IL4R and PROK1, PTX3, POF1B, FCRL1, SOD3, PGA4, ITM2A and EXTL1, SPP1, PLXDC2, COMP, L MNB2, TCL1A, PROK1 and IL4R, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A and PTPRS, SPP1, LMNB2, FCRL1, SOD3, PLXDC1, CDH23 and ADGRE5, SPP1, COMP, FCRL1, SOD3, TCL1A, LMNB2 and ADGRE1, SPP1, PLXDC2, COMP, LMNB2, TCL1A, IGFBP1 and PROK1, SPP1, PLXDC2, COMP, LMN B2, PROK1, TCL1A and CNTN1, PTX3, POF1B, FCRL1, SOD3, PGA4, ITM2A and PLXDC1, SPP1, PLXDC2, COMP, LMNB2, TCL1A, CLEC3B and PROK1, SPP1, PLXDC2, COMP, LMNB2, TCL1A, PROK1 and PTPRS, or PTX3, POF1B, THBS4, EXTL1, PGA4, SOD3 and ITM2A; that is, any one of the above 40 7-markers combinations.
优选地，所述7markers组合为所述E中的任意七种。Preferably, the 7 markers combination is any seven of the E.
优选地，所述7markers组合为：CEACAM5、COMP、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1与GDF15，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与GDF15，CEACAM5、COMP、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与GDF15，COMP、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1与GDF15，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1与GDF15，COMP、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC与GDF15，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、SERPINA1与EDA2R，COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1与EDA2R，TMPRSS15、COMP、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC与EDA2R，TMPRSS15、COMP、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG与EDA2R，CEACAM5、COMP、PTX3、AREG、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC与EDA2R，COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG与GDF15，CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、GDF15与EDA2R，COMP、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、SERPINA1与GDF15，COMP、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、AREG、TNC、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1与GDF15，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与EDA2R，CEACAM5、COMP、FCRL1、AREG、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与GDF15，CEACAM5、COMP、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1与EDA2R，TMPRSS15、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、COMP、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、GDF15与EDA2R，CEACAM5、COMP、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1与GDF15，COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1与EDA2R，CEACAM5、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1与GDF15，TMPRSS15、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、GDF15与EDA2R，COMP、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1与EDA2R，FCRL1、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC与SERPINA1，TMPRSS15、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG与TNC，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1与GDF15，COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1、GDF15，CEACAM5、COMP、PTX3、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1、SERPINA1与EDA2R，CEACAM5、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，FCRL1、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、GDF15与EDA2R，CEACAM5、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC与GDF15，CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，PTX3、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、SERPINA1与GDF15，CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG与NOTCH1，TMPRSS15、CEACAM5、COMP、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC与SERPINA1，TMPRSS15、CEACAM5、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、GDF15与EDA2R，TMPRSS15、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC与NOTCH1，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、SERPINA1与GDF15，CEACAM5、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、SERPINA1与GDF15，CEACAM5、COMP、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC与SERPINA1，TMPRSS15、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC与NOTCH1，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与SERPINA1，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、TNC、SERPINA1与GDF15，FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC与NOTCH1，CEACAM5、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1与SERPINA1，CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与SERPINA1，FCRL1、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1与SERPINA1，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC与SERPINA1，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，CEACAM5、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，或CEACAM5、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R。Preferably, the 7 markers combination is: CEACAM5, COMP, PTX3, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1 and GDF15, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1 and GDF15, CEACAM5, COMP, PTX3, AREG, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG, TNC and EDA2R, CO MP, FCRL1, PTX3, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, and GDF15, COMP, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3 , AREG, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, and GDF15, CEACAM5, COMP, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, NOTCH1, and GDF15, CEACAM5, COMP, FCRL1, PTX3, TNC, NOT CH1 and GDF15, TMPRSS15, COMP, PTX3, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1 and GDF15, COMP, PTX3, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS 15, COMP, FCRL1, PTX3, TNC, GDF15, and EDA2R, COMP, FCRL1, PTX3, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, AREG, TNC, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG, NOTCH1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, TNC, NOTCH1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, TNC, SERPINA1, and EDA2R, COMP, PTX3, AREG, TNC, NOTCH1, SERPINA1 AND GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG, NOTCH1, AND EDA2R, TMPRSS15, COMP, PTX3, TNC, NOTCH1, SERPINA1 AND GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, AND EDA2R, TMPRSS15, COMP, PTX3, AREG, NOTCH1, GDF15, AND EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, NOTCH1, GDF15, TMPRS S15, COMP, FCRL1, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, and EDA2R, CEACAM5, COMP, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, SERPINA1, and EDA2R, TMPRSS15, CE ACAM5, COMP, PTX3, AREG, TNC, and EDA2R, COMP, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, TNC, GDF15, and EDA2R, COMP, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, ARE G, TNC and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG and GDF15, CEACAM5, COMP, FCRL1, TNC, NOTCH1, SERPINA1 and GDF15, TMPRSS15, COMP, FCRL1, PTX3, TNC, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, GDF15 and EDA 2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, NOTCH1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, GDF15, and EDA2R, COMP, FC RL1, PTX3, AREG, TNC, NOTCH1, and GDF15, TMPRSS15, COMP, PTX3, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, TNC, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, PTX3, N OTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, PTX3, AREG, TNC, NOTCH1 and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1 and GDF15, TMPRSS15, COMP, PTX3, TNC, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, PTX3, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, and EDA2R, COMP, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, AREG, SERPINA1 , GDF15 and EDA2R, TMPRSS15, PTX3, AREG, TNC, NOTCH1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, GDF15 and EDA2R, COMP, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, AREG, TNC, NOTCH1, SERPINA1 and GDF15 , TMPRSS15, CEACAM5, COMP, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, NOTCH1, GDF15, and EDA2R , TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG, SERPINA1, and GDF15, TMPRSS15, FCRL1, PTX3, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and EDA2R, TMPRSS15 ,CEACAM5,COMP,FCRL1,TNC,SERPINA1,AND GDF15,COMP,FCRL1,PTX3,AREG,TNC,GDF15AND EDA2R,CEACAM5,COMP,FCRL1,AREG,NOTCH1,SERPINA1AND EDA2R,TMPRSS15,COMP,FCRL1,TNC,NOTCH1,SERPINA1AND GDF15,TMPRSS15,CEACAM5,COMP,TNC,NOTCH1,GDF15AND EDA2R,COMP,FCRL1,AREG,T NC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, SERPINA1, and GDF15, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, and GDF15, TMPRSS15, COMP, FCRL1, AREG, TNC, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, AREG, NOTCH1, SE RPINA1 and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, SERPINA1 and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, NOTCH1 and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, NOTCH1 and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1 AND GDF15,COMP,FCRL1,PTX3,AREG,TNC,NOTCH1ANDEDA2R,CEACAM5,COMP,TNC,NOTCH1,SERPINA1,GDF15ANDEDA2R,TMPRSS15,COMP,FCRL1,NOTCH1,SERPINA1,GDF15ANDEDA2R,TMPRSS15,CEACAM5,COMP,AREG,TNC,NOTCH1ANDEDA2R,CEACAM5,COMP,FCRL1,PTX3,AREG,TNCANDEDA2R,CEACAM5,C OMP, FCRL1, AREG, NOTCH1, GDF15, and EDA2R, COMP, FCRL1, PTX3, AREG, SERPINA1, GDF15, and EDA2R, COMP, FCRL1, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, SERPINA1, GDF15, CEACAM5, COMP, FCRL1, TNC , NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, TNC, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, SERPINA1, and GDF15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, and GDF15, CEACAM5, COMP, FCRL1, PTX3, TNC, SERPIN A1 and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, TNC, NOTCH1 and GDF15, TMPRSS15, COMP, FCRL1, AREG, NOTCH1, SERPINA1 and EDA2R, CEACAM5, COMP, AREG, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, PTX3, AREG, TNC, NOTCH1, SERPINA1 and GDF15, CEACAM5, COMP, FCRL1, PTX3, AREG, SERPINA1 and EDA2R, TMPRSS15, COMP, PTX3, AREG, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, SERPINA1, and GDF15, TM PRSS15, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, NOTCH1, and EDA2R, TMPRSS15, COMP, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPR SS15, COMP, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, PTX3, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, SERPINA1, and GDF15, TM PRSS15, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, PTX3, AREG, TNC, SERPINA1, and GDF15, CEACAM5, COMP, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, NOTCH1, SERPINA1, and GDF15, COMP 、FCRL1、AREG、TNC、NOTCH1、GDF15和EDA2R，COMP、FCRL1、TNC、NOTCH1、SERPINA1、GDF15和EDA2R，CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1和EDA2R，CEACAM5、COMP、FCRL1、PTX3、SERPINA1、GDF15和EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1和EDA2R，TMPRSS15、COMP、TN C, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15 , CEACAM5, COMP, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, GDF15, and EDA2R, CEACAM5, COMP, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, and GDF15, COMP, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, COMP 、AREG、NOTCH1、SERPINA1、GDF15和EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1、SERPINA1和GDF15，CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1和GDF15，TMPRSS15、CEACAM5、COMP、PTX3、TNC、SERPINA1和EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1和EDA2R，CEACAM5、PTX3、 TNC、NOTCH1、SERPINA1、GDF15和EDA2R，TMPRSS15、COMP、FCRL1、TNC、NOTCH1、SERPINA1和EDA2R，FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15和EDA2R，COMP、AREG、TNC、NOTCH1、SERPINA1、GDF15和EDA2R，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1、GDF15和EDA2R，CEACAM5、COMP、PTX3、ARE G, TNC, NOTCH1, and EDA2R, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, and GDF15, TMPRSS15, FCRL1, TNC, NOTC H1、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、TNC、NOT CH1, SERPINA1 and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, GDF15 and EDA2R, COMP, FCRL1, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1 and GDF15, T MPRSS15, COMP, PTX3, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, and EDA2R, FCRL1, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, NOTCH1, SERPINA1, GDF15, and EDA2R, S15, CEACAM5, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, and SERPINA1, TMPRSS15, PTX3, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, COMP, PTX3, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, NOTCH1, SERPINA1, GDF15, and EDA2R, TMP RSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, and TNC, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, and GDF15, COMP, FCRL1, PTX3, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, CEACAM5, COMP, PTX3, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, GDF15, CEACAM5, COMP, PTX3, AREG, SERP INA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, SERPINA1 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1, SERPINA1 and GDF15, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1 and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, NOTCH1, SERPINA1 and EDA2R, CEACAM5, PTX3, AREG, TNC, NOTCH1, GDF 15 and EDA2R, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, GDF15 and EDA2R, CEACAM5, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, FCRL1, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, TNC, NOTCH1 and EDA2R, TMPRSS15, COMP, AREG, TNC, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, TNC, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, GDF15 and EDA2R, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1 and EDA2R, CEACAM5, COMP, FCRL1, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS1 5.CEACAM5,FCRL1,PTX3,TNC,GDF15,AND EDA2R,COMP,FCRL1,PTX3,AREG,TNC,SERPINA1,AND EDA2R,TMPRSS15,CEACAM5,PTX3,AREG,NOTCH1,GDF15,AND EDA2R,TMPRSS15,CEACAM5,COMP,FCRL1,AREG,TNC,AND SERPINA1,TMPRSS15,CEACAM5,FCRL1,PTX3,AREG,TNC,AND GDF15,CEACAM5,COMP,PTX3, AREG, TNC, SERPINA1, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, NOTCH1 , GDF15 and EDA2R, COMP, FCRL1, AREG, TNC, SERPINA1, GDF15 and EDA2R, TMPRSS15, AREG, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, PTX3, AREG, TNC, NOTCH1, SERPINA1, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, SERPIN A1 and GDF15, CEACAM5, PTX3, AREG, TNC, NOTCH1, SERPINA1 and GDF15, TMPRSS15, FCRL1, PTX3, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG and NOTCH1, TMPRSS15, CEACAM5, COMP, AREG, SERPINA1, GDF15 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1 and ED A2R, CEACAM5, COMP, FCRL1, AREG, TNC, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, PTX3, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, and SERPINA1, TMPR SS15, CEACAM5, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, COMP, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, FCRL1, PTX3, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, FCRL1, PTX3, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, GDF15, and EDA2R, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, SERPINA1, GDF15, and EDA2R, CEACAM5, F CRL1, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, and NOTCH1, TMPRSS15, CEACAM5, COMP, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, SERPINA1, and EDA2R, TMPRSS15, C EACAM5, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, SERPINA1, and GDF15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15 , CEACAM5, COMP, FCRL1, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, NOTCH1, SERPINA1, and EDA2 R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, TNC, SERPINA1, GDF15, and ED A2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, SERPINA1, and GDF15, CEACAM5, COMP, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, SERPINA1, and GDF15, CEACAM5, COMP, AREG, TNC, SERPINA1, and GDF15, CEACAM5, COMP, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG, TNC, and SERPINA1, TMPRSS15, FCRL1, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, and NOTCH1, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, and SERPINA1, TMPR SS15, CEACAM5, COMP, PTX3, AREG, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, PTX3, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, PTX3, AREG, TNC, SERPINA1, and GDF15, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS 15, COMP, FCRL1, PTX3, AREG, TNC, and NOTCH1, CEACAM5, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, and SERPINA1, CEACAM5, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, and SERPINA1, FCRL1, AREG, TNC , NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, NOTCH1, and SERPINA1, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1, SERPINA1, and EDA2R, CEACAM5, FCRL1, PTX 3, AREG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, A REG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1, and SERPINA1, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, COMP, FCRL1, PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FC RL1, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, and SERPINA1, TMPRSS15, COMP, PTX3, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, and SERPINA1, CEACAM5, FCRL1, AREG , TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, and SERPINA1, CEACAM5, FCRL1, PTX3, AREG, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, AREG, TN C, SERPINA1 and EDA2R, FCRL1, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, GDF15 and EDA2R, CEACAM5, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R, or CEACAM5, FCRL1, AREG, TNC, SERPINA1, GDF15 and EDA2R.
优选地，所述A包含8markers组合，所述8markers组合为所述B中的任意八种。Preferably, the A comprises a combination of 8 markers, and the combination of 8 markers is any eight of the combinations in B.
优选地，所述8markers组合为f1)和f2):Preferably, the 8 markers are combined into f1) and f2):
f1)所述7markers组合(优选上述40个7markers组合中的任一种)；f1) the 7 markers combination (preferably any one of the above 40 7 markers combinations);
f2)所述B中的任意一种；f2) any one of the above B;
所述f2)不同于f1)中所述7markers组合中的任意一个marker。The f2) is different from any marker in the combination of 7 markers in f1).
优选地，所述8markers组合为：PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、SOD3与ITM2A，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、SOD3与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与COMP，PTX3、POF1B、THBS4、EXTL1、PGA4、SOD3、ITM2A与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与SOD3，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与BAG3，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与ADGRE1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与ADGRE1，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与SOD3，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与AREG，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与ADGRE5，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与BAG3，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与COMP，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与HMCN2，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、SOD3与PROK1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与COMP，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与NT5C1A，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与LBP，PTX3、POF1B、THBS4、EXTL1、PGA4、SOD3、ITM2A与ADGRE1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与SPON2，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与CDH23，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与PTPRS，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与FCER2，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与CCL7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与TNC，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、FCER2与TNC，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与CKAP4，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与FCER2，PTX3、POF1B、THBS4、EXTL1、PGA4、SOD3、ITM2A与PROK1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与CEACAM5，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与IFNL1，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与TNC，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与BAG3，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与NOS2，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与C9，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与IL4R，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与SOD3，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与IGFBP1，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、NPY与CEACAM16，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与CCL7，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、FCER2与BAG3，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与TNC，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、NPY与PTPRS，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与NPY，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与NPY，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与AGR3，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与CEACAM16，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、NPY与TNC，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与PROK1，SPP1、LMNB2、SOD3、ADGRE5、PLXDC1、PROK1、LBP与FASLG，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、FCER2与IGFBP1，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、NPY与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与NT5C1A，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与IGFBP1，PTX3、POF1B、THBS4、FASLG、ITM2A、EXTL1、TNC与PROK1，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与NPY，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与TNFRSF10B，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、PTPRS与ADGRE1，PTX3、POF1B、THBS4、EXTL1、PGA4、SOD3、PROK1与ITM2A，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与ITGB7，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与C9，PTX3、POF1B、THBS4、ADGRE5、PGA4、ITM2A、NPY与ADGRE1，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、AGR3与PCDH7，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与LPL，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与NOS2，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与AGR3，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1与DLK1，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与TMPRSS15，PTX3、POF1B、THBS4、EXTL1、PGA4、ADGRE1、ITM2A与CEACAM16，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与TNFRSF10B，PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、SOD3与ADGRE1，或PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PCDH7与GCG。Preferably, the 8 markers combination is: PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and PCDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, SOD3 and ITM2A, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, SOD3 and PCDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and COMP, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and COMP. BS4, EXTL1, PGA4, SOD3, ITM2A and PCDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and SOD3, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and BAG3, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and PCDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and ADG RE1, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and ADGRE1, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and SOD3, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and AREG, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and ADGRE5, PTX3, POF1B, THBS4, EXTL1, P GA4, ITM2A, PROK1 and BAG3, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and COMP, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and HMCN2, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, SOD3 and PROK1, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and COMP, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and NT5C1A, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and LBP, PTX3, POF1B, THBS4, EXTL1, PGA4, SOD3, ITM2A and ADGRE1, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and SPON2, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and C DH23, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and PTPRS, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and FCER2, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and CCL7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and TNC, PTX3, POF1B, THBS4, ADGRE5, PG A4, ITM2A, FCER2 and TNC, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and CKAP4, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and FCER2, PTX3, POF1B, THBS4, EXTL1, PGA4, SOD3, ITM2A and PROK1, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and CEACAM5, PTX3, POF1 B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and IFNL1, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and TNC, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and BAG3, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and NOS2, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and C9 , PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and IL4R, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and SOD3, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and IGFBP1, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, NPY and CEACAM16, PTX3, POF1B, THBS4, EXTL1, PGA 4, ITM2A, PCDH7 and CCL7, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, FCER2 and BAG3, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and TNC, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, NPY and PTPRS, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and NPY, PTX3, POF1B, THBS 4, EXTL1, PGA4, ITM2A, PROK1 and NPY, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and AGR3, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and CEACAM16, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, NPY and TNC, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and PROK1, S PP1, LMNB2, SOD3, ADGRE5, PLXDC1, PROK1, LBP and FASLG, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, FCER2 and IGFBP1, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, NPY and PCDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and NT5C1A, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A TM2A, PCDH7 and IGFBP1, PTX3, POF1B, THBS4, FASLG, ITM2A, EXTL1, TNC and PROK1, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and NPY, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and TNFRSF10B, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, PTPRS and ADGRE1, PTX3, P OF1B, THBS4, EXTL1, PGA4, SOD3, PROK1, and ITM2A, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7, and ITGB7, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1, and C9, PTX3, POF1B, THBS4, ADGRE5, PGA4, ITM2A, NPY, and ADGRE1, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, AGR3, and P CDH7, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and LPL, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and NOS2, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and AGR3, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and DLK1, PTX3, POF1B, THBS4, EXTL1, PGA4 , ADGRE1, ITM2A and TMPRSS15, PTX3, POF1B, THBS4, EXTL1, PGA4, ADGRE1, ITM2A and CEACAM16, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and TNFRSF10B, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, SOD3 and ADGRE1, or PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PCDH7 and GCG.
优选地，所述8markers组合为所述E中的任意八种。Preferably, the 8 markers are combined into any eight of the E.
优选地，所述8markers组合为：TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与GDF15，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与GDF15，COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、SERPINA1与GDF15，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1与GDF15，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，COMP、FCRL1、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、PTX3、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、COMP、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1与GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1与GDF15，TMPRSS15、CEACAM5、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1、GDF15与EDA2R，COMP、FCRL1、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1、SERPINA1与GDF15，CEACAM5、COMP、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1、GDF15与EDA2R，TMPRSS15、FCRL1、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、SERPINA1、GDF15与EDA2R，COMP、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与NOTCH1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、FCRL1、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、PTX3、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、NOTCH1、SERPINA1与EDA2R，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与GDF15，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、TNC与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、AREG、TNC、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、SERPINA1与GDF15，CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1、SERPINA1与EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、PTX3、AREG、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，TMPRSS15、CEACAM5、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R，CEACAM5、FCRL1、AREG、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，CEACAM5、COMP、FCRL1、PTX3、AREG、TNC、NOTCH1与SERPINA1，或CEACAM5、FCRL1、PTX3、AREG、TNC、SERPINA1、GDF15与EDA2R。Preferably, the 8 markers are combined as follows: TMPRSS15, COMP, FCRL1, PTX3, TNC, NOTCH1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, GDF15 and EDA2R, TMP RSS15, COMP, FCRL1, PTX3, AREG, TNC, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1, GDF15, and EDA2R, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG, NOTCH1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, FCRL1, PTX3, AREG, TNC, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, and G DF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, CO MP, FCRL1, PTX3, AREG, NOTCH1, GDF15, TMPRSS15, COMP, FCRL1, AREG, TNC, NOTCH1, GDF15, EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, NOTCH1, GDF15, EDA2R, CEACAM5, COMP, PTX3, TNC, NOTCH1, SERPINA1, GDF15, EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, NO TCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, COMP, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and EDA2 R,TMPRSS15,COMP,FCRL1,PTX3,AREG,TNC,NOTCH1,AND GDF15,TMPRSS15,CEACAM5,COMP,FCRL1,TNC,NOTCH1,GDF15AND EDA2R,COMP,FCRL1,PTX3,AREG,NOTCH1,SERPINA1,GDF15AND EDA2R,TMPRSS15,CEACAM5,COMP,FCRL1,PTX3,AREG,TNC,AND GDF15,COMP,PTX3,AREG,TNC,NOTCH1,SERPINA1,GDF15AND EDA2R,TMPRSS15,COMP,FCRL1, PTX3, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, SERPINA1, and EDA2R, TMPRSS15, COMP, FCRL1, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX 3、AREG、SERPINA1与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、NOTCH1、SERPINA1、GDF15与EDA2R，COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、AREG、SERPINA1、GDF15与EDA2R，TMPRSS15、COMP、FCRL1、PTX3、TNC、NOTCH1、SERPINA1、GDF15与EDA2R，TMPRSS15、CEACAM5、COMP、PTX3、AREG、NOTCH 1.SERPINA1 and GDF15,TMPRSS15,COMP,FCRL1,PTX3,AREG,NOTCH1,SERPINA1 and EDA2R,TMPRSS15,CEACAM5,COMP,PTX3,TNC,SERPINA1,GDF15 and EDA2R,TMPRSS15,COMP,PTX3,TNC,NOTCH1,SERPINA1,GDF15 and EDA2R,TMPRSS15,CEACAM5,COMP,FCRL1,AREG,TNC,SERPINA1 and EDA2R,TMPRSS15,CEACAM5,COMP,FCRL1,PTX3,AREG,NOT CH1 and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, SERPINA1 and GDF15, TMPRSS15, COMP, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, NOTCH1, SERPINA1 and GDF15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1 and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, SERPINA1 and GDF15 , TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, AREG, TNC, SERPINA1, and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and GDF15, TMPRS S15, CEACAM5, COMP, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, SERPINA1, and GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEA CAM5, COMP, FCRL1, PTX3, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, PTX3, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP, FCRL1, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, PTX3,AREG,NOTCH1,SERPINA1,GDF15,AND EDA2R,TMPRSS15,CEACAM5,COMP,PTX3,AREG,TNC,SERPINA1,AND GDF15,COMP,FCRL1,PTX3,AREG,TNC,NOTCH1,SERPINA1,AND GDF15,COMP,FCRL1,PTX3,AREG,TNC,SERPINA1,GDF15,COMP,FCRL1,PTX3,AREG,TNC,SERPINA1,GDF15,AND EDA2R,TMPRSS15,CEACAM5,COMP,AREG,TNC,NOTCH1,SERPINA1,AND EDA2R,TMPRSS15,COMP,FCRL1,PTX3,TNC, NOTCH1,SERPINA1,AND EDA2R,CEACAM5,COMP,FCRL1,AREG,TNC,NOTCH1,GDF15AND EDA2R,TMPRSS15,COMP,FCRL1,PTX3,AREG,TNC,SERPINA1,AND GDF15,TMPRSS15,COMP,FCRL1,AREG,NOTCH1,SERPINA1,GDF15AND EDA2R,TMPRSS15,CEACAM5,COMP,FCRL1,AREG,TNC,GDF15AND EDA2R,TMPRSS15,COMP,FCRL1,PTX3,AREG,NOTCH1,SERPINA1 with GDF15, TMPRSS15, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1 with GDF15, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, SERPINA1 with EDA2R, TMPRSS15, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, NOTCH1, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, AREG, NOTCH1, SERPINA1, GDF15 with EDA2R, CEACAM5, COMP, AREG, TNC, NOTCH1, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1, GDF15 with EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, NOTCH1, SERPINA 1 and EDA2R, CEACAM5, COMP, FCRL1, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, PTX3, AREG, TNC, NOTCH1, SERPINA1 and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, SERPINA1 and EDA2R, TMPRSS15, COMP, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, GDF15 and EDA2R, CEACA M5, COMP, FCRL1, PTX3, TNC, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, COMP, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, SERPINA1, and GDF15, CEACAM5, COMP, FCRL1, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, COMP 、FCRL1、AREG、TNC、NOTCH1、SERPINA1和EDA2R，TMPRSS15、CEACAM5、FCRL1、PTX3、NOTCH1、SERPINA1、GDF15和EDA2R，TMPRSS15、CEACAM5、COMP、FCRL1、AREG、TNC、SERPINA1和GDF15，TMPRSS15、CEACAM5、COMP、FCRL1、TNC、NOTCH1、SERPINA1和EDA2R，TMPRSS15、CEACAM5、PTX3、AREG、TNC、NOTCH1、SERPINA1和GDF15，CEACAM5、COM P, FCRL1, PTX3, AREG, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AR EG, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, GDF15, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, NO TCH1 and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, AREG, TNC, SERPINA1, GDF15 and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, GDF15 and EDA2R, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, SERPINA1 and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, GDF15 and EDA2 R, COMP, FCRL1, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, COMP, PTX3, AREG, TNC, SERPINA1, GDF15, and EDA2R, CEACAM5, F CRL1, PTX3, AREG, TNC, NOTCH1, GDF15, and EDA2R, TMPRSS15, FCRL1, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, SERPINA1, GDF15, and EDA2R, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, F CRL1, PTX3, AREG, TNC, and NOTCH1, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, FCRL1, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, SERPINA1, GDF15, and EDA2R, TMPRSS15, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, NOTCH1, SERPINA1, GDF15, and EDA2R, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, GDF15, and EDA2R. CH1, SERPINA1, and GDF15, TMPRSS15, CEACAM5, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, PTX3, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3 , AREG, TNC, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, SERPINA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, AREG, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, TNC, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, AREG, TNC, SERP INA1, GDF15, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1, and GDF15, CEACAM5, FCRL1, PTX3, AREG, TNC, NOTCH1, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1, and EDA2R, TMPRSS15, CEACAM5, COMP, FCRL1, PTX3, AREG, NOTCH1, and SERPINA1, TMPRSS15, CEACAM5, FCRL1, PTX3, AREG, TNC, NOT CH1 and SERPINA1, TMPRSS15, CEACAM5, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R, CEACAM5, FCRL1, AREG, TNC, NOTCH1, SERPINA1, GDF15 and EDA2R, TMPRSS15, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1 and SERPINA1, CEACAM5, COMP, FCRL1, PTX3, AREG, TNC, NOTCH1 and SERPINA1, or CEACAM5, FCRL1, PTX3, AREG, TNC, SERPINA1, GDF15 and EDA2R.
优选地，所述A还包含K中的至少一种，所述K与所述A的并集为所述B，且所述K与所述A无交集(比如：所述A包含FCRL1，则K为不包含FCRL1的B)。Preferably, A also includes at least one of K, the union of K and A is B, and K and A have no intersection (for example, if A includes FCRL1, then K is B that does not include FCRL1).
优选地，所述产品的受试样品选自待测对象的体液、组织、细胞、排泄物中的至少一种；进一步为体液。Preferably, the test sample of the product is selected from at least one of body fluids, tissues, cells, and excrement of the subject to be tested; further, it is body fluid.
优选地，所述体液包含血液、淋巴液、胸水、脑脊液、关节液、腹水、唾液、淋巴液、体内积液中的至少一种；进一步为血液。Preferably, the body fluid comprises at least one of blood, lymph, pleural effusion, cerebrospinal fluid, joint fluid, ascites, saliva, lymph, and body fluid; further comprising blood.
优选地，所述组织包含肠粘膜组织。Preferably, the tissue comprises intestinal mucosal tissue.
优选地，所述血液包括血清、血浆、干血斑、全血中的至少一种；进一步为血清。Preferably, the blood comprises at least one of serum, plasma, dried blood spots and whole blood; further comprises serum.
优选地，所述排泄物包含尿液、粪便、泪液、汗液中的至少一种。Preferably, the excrement includes at least one of urine, feces, tears and sweat.
优选地，所述受试样品选自待测对象的血清。Preferably, the test sample is selected from the serum of the subject to be tested.
优选地，所述待测对象包含哺乳动物，例如人类、非人灵长类动物(例如猩猩、猿)、啮齿动物(例如大鼠、小鼠、豚鼠)、宠物(例如猫、狗)、家畜(例如马、牛、羊、猪、兔)。Preferably, the subject to be tested includes mammals, such as humans, non-human primates (such as gorillas, apes), rodents (such as rats, mice, guinea pigs), pets (such as cats, dogs), and livestock (such as horses, cows, sheep, pigs, rabbits).
优选地，所述待测对象包含人类。Preferably, the subject to be tested includes humans.
优选地，所述检测标志物的物质包含定量检测标志物的物质。Preferably, the substance for detecting a marker comprises a substance for quantitatively detecting a marker.
优选地，所述检测标志物的物质包含在基因水平和/或蛋白质水平上检测标志物的物质。Preferably, the substance for detecting a marker comprises a substance for detecting a marker at a gene level and/or a protein level.
优选地，所述物质包含用于选自下组的一种或多种检测技术或方法中的物质：免疫组织化学法、Western印迹法、Northern印迹法、PCR、生物芯片法、核酸测序法、氨基酸测序法、高效液相色谱法、毛细管凝胶电泳法、近红外光谱法、质谱法、表面等离子共振技术、免疫-PCR技术、生物素-亲和素技术。Preferably, the substance comprises a substance for one or more detection techniques or methods selected from the following group: immunohistochemistry, Western blotting, Northern blotting, PCR, biochip method, nucleic acid sequencing, amino acid sequencing, high performance liquid chromatography, capillary gel electrophoresis, near infrared spectroscopy, mass spectrometry, surface plasmon resonance technology, immuno-PCR technology, biotin-avidin technology.
优选地，所述免疫组化学法包含酶联免疫吸附法、免疫荧光法、放射免疫测定法、免疫共沉淀法、免疫化学发光法、胶体金免疫技术、荧光免疫层析技术、补体结合分析法、流式细胞荧光分辨、单分子检测技术中的至少一种；进一步为酶联免疫吸附法；更进一步为双抗体夹心法。Preferably, the immunohistochemistry method comprises at least one of enzyme-linked immunosorbent assay, immunofluorescence assay, radioimmunoassay, co-immunoprecipitation, immunochemiluminescence, colloidal gold immunoassay, fluorescent immunochromatography, complement fixation analysis, flow cytometry fluorescence resolution, and single molecule detection technology; further, enzyme-linked immunosorbent assay; and further, double antibody sandwich method.
优选地，所述检测标志物的物质选自：对标志物具有特异性的物质、标志物特异性的探针、基因芯片、蛋白质芯片、PCR引物中的一种或多种。Preferably, the substance for detecting the marker is selected from: one or more of a substance specific to the marker, a marker-specific probe, a gene chip, a protein chip, and a PCR primer.
优选地，所述对标志物具有特异性的物质包含h1)～h4)中的任一种：Preferably, the substance specific to the marker comprises any one of h1) to h4):
h1)特异性结合标志物的抗体；h1) an antibody that specifically binds to a marker;
h2)特异性结合标志物的配体蛋白或多肽；h2) a ligand protein or polypeptide that specifically binds to the marker;
h3)特异性识别标志物的非蛋白类化合物；h3) non-protein compounds that specifically recognize markers;
h4)特异性识别标志物的核酸适配体。h4) Nucleic acid aptamers that specifically recognize markers.
优选地，所述抗体包含多克隆抗体、单克隆抗体、单链抗体、功能性抗体片段、抗体Fab区，纳米抗体、嵌合抗体、多特异性抗体中的至少一种。Preferably, the antibody comprises at least one of a polyclonal antibody, a monoclonal antibody, a single-chain antibody, a functional antibody fragment, an antibody Fab region, a nanobody, a chimeric antibody, and a multispecific antibody.
优选地，所述产品包含试剂、试剂盒、试纸、芯片、装置、系统中的至少一种。Preferably, the product comprises at least one of a reagent, a kit, a test paper, a chip, a device, and a system.
优选地，所述产品还包含检测其他用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的标志物的物质，比如标志物可以是CN114959028A公开的SNORD15B和SNORA5C、CN109852698A公开的环指蛋白32、CN111848773A公开的RANBP1等。Preferably, the product also contains substances for detecting other markers used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer, such as SNORD15B and SNORA5C disclosed in CN114959028A, RING finger protein 32 disclosed in CN109852698A, RANBP1 disclosed in CN111848773A, etc.
优选地，所述产品还包含基因表达量辅助检测试剂，所述基因表达量辅助检测试剂包括：使引物对应的扩增子可视化的反应试剂、RNA提取试剂、逆转录试剂、cDNA扩增试剂、制备标准曲线所用的标准品、阳性对照品中的至少一种。Preferably, the product further comprises auxiliary detection reagents for gene expression, and the auxiliary detection reagents for gene expression include: a reaction reagent for visualizing the amplicon corresponding to the primer, an RNA extraction reagent, a reverse transcription reagent, a cDNA amplification reagent, a standard substance used to prepare a standard curve, and at least one of a positive control substance.
优选地，所述产品还包含蛋白表达量辅助检测试剂，所述蛋白表达量辅助检测试剂包括显色剂、封闭液、抗体稀释液、洗涤缓冲液、显色终止液、制备标准曲线所用的标准品、阳性对照品中的至少一种。Preferably, the product further comprises an auxiliary detection reagent for protein expression, and the auxiliary detection reagent for protein expression comprises at least one of a color developer, a blocking solution, an antibody diluent, a washing buffer, a color stop solution, a standard substance used to prepare a standard curve, and a positive control substance.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明的第二个方面，提供一种标志物组合，所述标志物组合包含本发明第一个方面中所述的B中的至少两种，可以是B中2种、3种、4种、5种、6种、7种、8种、9种、10种、11种、12种、13种、14种、15种、16种、17种、18种、19种、20种、21种、22种、23种、24种、25种、26种、27种、28种、29种、30种、31种、32种、33种、34种、35种、36种、37种、38种、39种、40种、41种、42种、43种、44种、45种、46种、47种、48种、49种、50种、51种、52种、53种、54种、55种、56种、57种、58种、59种、60种、61种、62种、63种、64种、65种、66种、67种、68种、69种、70种、71种、72种、73种、74种、75种、76种、77种、78种、79种、80种、81种、82种、83种、84种、85种、86种、87种、88种、89种、或90种。In a second aspect of the present invention, a marker combination is provided, wherein the marker combination comprises at least two of B described in the first aspect of the present invention, and may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, or 90 kinds.
优选地，所述标志物组合包含：Preferably, the marker combination comprises:
k1)FCRL1；和k1) FCRL1; and
k2)所述B中的至少一种；k2) at least one of the B;
所述k2)中的任意一个marker不同于所述k1)。Any marker in k2) is different from k1).
优选地，所述标志物组合包含：Preferably, the marker combination comprises:
j1)AREG；和j1)AREG; and
j2)所述B中的至少一种；j2) at least one of the B;
所述j2)中的任意一个marker不同于所述j1)。Any marker in j2) is different from j1).
优选地，所述标志物组合包含所述B中的任意2种、3种、4种、5种、6种、7种、或8种。Preferably, the marker combination comprises any 2, 3, 4, 5, 6, 7, or 8 of the B.
优选地，所述标志物组合包含本发明第一个方面中的2markers组合、3markers组合、4markers组合、5markers组合、6markers组合、7markers组合或8markers组合。Preferably, the marker combination comprises a 2-markers combination, a 3-markers combination, a 4-markers combination, a 5-markers combination, a 6-markers combination, a 7-markers combination or an 8-markers combination in the first aspect of the present invention.
优选地，所述标志物组合还包含检测其他用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的标志物，比如标志物可以是CN114959028A公开的SNORD15B和SNORA5C、CN109852698A公开的环指蛋白32、CN111848773A公开的RANBP1等。Preferably, the marker combination also includes detecting other markers for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer, for example, the markers may be SNORD15B and SNORA5C disclosed in CN114959028A, RING finger protein 32 disclosed in CN109852698A, RANBP1 disclosed in CN111848773A, etc.
优选地，所述标志物组合用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估。Preferably, the marker combination is used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
优选地，所述标志物组合来自待测对象的体液、组织、细胞、排泄物中的至少一种；进一步为体液。Preferably, the marker combination is from at least one of the body fluids, tissues, cells, and excreta of the subject to be tested; further, the body fluids.
优选地，所述待测对象、体液、组织、细胞、或排泄物为本发明第一个方面中的待测对象、体液、组织、细胞、或排泄物。Preferably, the object to be detected, body fluid, tissue, cell, or excrement is the object to be detected, body fluid, tissue, cell, or excrement in the first aspect of the present invention.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明第三个方面，在于提供一种产品，包含检测本发明第二个方面的标志物组合的物质。The third aspect of the present invention is to provide a product comprising substances for detecting the marker combination of the second aspect of the present invention.
优选地，所述产品用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估。Preferably, the product is used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
优选地，所述检测标志物组合的物质包含定量检测标志物组合的物质。Preferably, the substance for detecting the marker combination comprises a substance for quantitatively detecting the marker combination.
优选地，所述检测标志物组合的物质包含在基因水平和/或蛋白质水平上检测标志物组合的物质。Preferably, the substance for detecting a marker combination comprises a substance for detecting a marker combination at a gene level and/or a protein level.
优选地，所述物质包含用于选自下组的一种或多种检测技术或方法中的物质：免疫组织化学法、Western印迹法、Northern印迹法、PCR、生物芯片法、核酸测序法、氨基酸测序法、高效液相色谱法、毛细管凝胶电泳法、近红外光谱法、质谱法、表面等离子共振技术、免疫-PCR技术、生物素-亲和素技术。Preferably, the substance comprises a substance for one or more detection techniques or methods selected from the following group: immunohistochemistry, Western blotting, Northern blotting, PCR, biochip method, nucleic acid sequencing, amino acid sequencing, high performance liquid chromatography, capillary gel electrophoresis, near infrared spectroscopy, mass spectrometry, surface plasmon resonance technology, immuno-PCR technology, biotin-avidin technology.
优选地，所述免疫组化学法包含酶联免疫吸附法、免疫荧光法、放射免疫测定法、免疫共沉淀法、免疫化学发光法、胶体金免疫技术、荧光免疫层析技术、补体结合分析法、流式细胞荧光分辨、单分子检测技术中的至少一种；进一步为酶联免疫吸附法；更进一步为双抗体夹心法。Preferably, the immunohistochemistry method comprises at least one of enzyme-linked immunosorbent assay, immunofluorescence assay, radioimmunoassay, co-immunoprecipitation, immunochemiluminescence, colloidal gold immunoassay, fluorescent immunochromatography, complement fixation analysis, flow cytometry fluorescence resolution, and single molecule detection technology; further, enzyme-linked immunosorbent assay; and further, double antibody sandwich method.
优选地，所述检测标志物组合的物质选自：对标志物具有特异性的物质、标志物特异性的探针、基因芯片、蛋白质芯片、PCR引物中的一种或多种。Preferably, the substance for detecting the marker combination is selected from: one or more of a substance specific to the marker, a marker-specific probe, a gene chip, a protein chip, and a PCR primer.
优选地，所述对标志物具有特异性的物质包含h1)～h4)中的任一种：Preferably, the substance specific to the marker comprises any one of h1) to h4):
h1)特异性结合标志物的抗体；h1) an antibody that specifically binds to the marker;
h2)特异性结合标志物的配体蛋白或多肽；h2) a ligand protein or polypeptide that specifically binds to the marker;
h3)特异性识别标志物的非蛋白类化合物；h3) non-protein compounds that specifically recognize markers;
h4)特异性识别标志物的核酸适配体。h4) Nucleic acid aptamers that specifically recognize markers.
优选地，所述抗体包含多克隆抗体、单克隆抗体、单链抗体、功能性抗体片段、抗体Fab区，纳米抗体、嵌合抗体、多特异性抗体中的至少一种。Preferably, the antibody comprises at least one of a polyclonal antibody, a monoclonal antibody, a single-chain antibody, a functional antibody fragment, an antibody Fab region, a nanobody, a chimeric antibody, and a multispecific antibody.
优选地，所述产品包含试剂、试剂盒、试纸、芯片、装置、系统中的至少一种。Preferably, the product comprises at least one of a reagent, a kit, a test paper, a chip, a device, and a system.
优选地，所述产品还包含检测其他用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的标志物的物质，比如标志物可以是CN114959028A公开的SNORD15B和SNORA5C、CN109852698A公开的环指蛋白32、CN111848773A公开的RANBP1等。Preferably, the product also contains substances for detecting other markers used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer, such as SNORD15B and SNORA5C disclosed in CN114959028A, RING finger protein 32 disclosed in CN109852698A, RANBP1 disclosed in CN111848773A, etc.
优选地，所述产品还包含基因表达量辅助检测试剂，所述基因表达量辅助检测试剂包括：使引物对应的扩增子可视化的反应试剂、RNA提取试剂、逆转录试剂、cDNA扩增试剂、制备标准曲线所用的标准品、阳性对照品中的至少一种。Preferably, the product further comprises auxiliary detection reagents for gene expression, and the auxiliary detection reagents for gene expression include: a reaction reagent for visualizing the amplicon corresponding to the primer, an RNA extraction reagent, a reverse transcription reagent, a cDNA amplification reagent, a standard substance used to prepare a standard curve, and at least one of a positive control substance.
优选地，所述产品还包含蛋白表达量辅助检测试剂，所述蛋白表达量辅助检测试剂包括显色剂、封闭液、抗体稀释液、洗涤缓冲液、显色终止液、制备标准曲线所用的标准品、阳性对照品中的至少一种。Preferably, the product further comprises an auxiliary detection reagent for protein expression, and the auxiliary detection reagent for protein expression comprises at least one of a color developer, a blocking solution, an antibody diluent, a washing buffer, a color stop solution, a standard substance used to prepare a standard curve, and a positive control substance.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明第四个方面，在于提供一种模型的构建方法，所述方法包含使用本发明第一个方面中的标志物进行模型构建的步骤。The fourth aspect of the present invention is to provide a method for constructing a model, which comprises the step of constructing a model using the markers in the first aspect of the present invention.
优选地，所述方法包含使用本发明第二个方面的标志物组合进行模型构建的步骤。Preferably, the method comprises the step of model building using the marker combination according to the second aspect of the invention.
优选地，所述模型用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估。Preferably, the model is used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
优选地，所述模型的构建的算法包含对数回归、线性判别分析、特征基因线性判别分析、支持向量机、随机森林(RandomRorest)、递归分区树、XGBoost、ShrunkenCentroids、StepAIC、Kth-Nearest Neighbor、Boosting、神经网络、贝叶斯网络、隐马尔可夫模型中的至少一种；进一步包含随机森林(RandomRorest)、XGBoost中的至少一种。Preferably, the algorithm for constructing the model includes at least one of logarithmic regression, linear discriminant analysis, eigengene linear discriminant analysis, support vector machine, random forest (RandomRorest), recursive partitioning tree, XGBoost, ShrunkenCentroids, StepAIC, Kth-Nearest Neighbor, Boosting, neural network, Bayesian network, and hidden Markov model; and further includes at least one of random forest (RandomRorest) and XGBoost.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明第五个方面，在于提供一种装置或系统，包含：A fifth aspect of the present invention is to provide a device or system, comprising:
检测模块：用于检测受试样品中本发明第一个方面中的标志物的含量、活性和/或表达量；和Detection module: used to detect the content, activity and/or expression of the marker in the first aspect of the present invention in the test sample; and
分析模块：用于将所述检测模块获取的数据输入根据本发明第四个方面的构建方法构建的模型进行分析。Analysis module: used for inputting the data acquired by the detection module into the model constructed according to the construction method of the fourth aspect of the present invention for analysis.
优选地，所述装置或系统用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估。Preferably, the device or system is used for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer.
优选地，所述检测模块用于检测受试样品中本发明第二个方面的标志物组合的含量、活性和/或表达量。Preferably, the detection module is used to detect the content, activity and/or expression level of the marker combination according to the second aspect of the present invention in the test sample.
优选地，所述受试样品为本发明第一个方面中的受试样品。Preferably, the test sample is the test sample in the first aspect of the present invention.
优选地，所述装置或系统还包含：输出模块，根据所述分析模块得到的分析结果，输出信息。Preferably, the device or system further comprises: an output module for outputting information according to the analysis result obtained by the analysis module.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明的第六个方面，提供一种计算机设备，所述计算机设备包括存储器和处理器，所述存储器存储有程序，所述处理器执行所述程序时实现如下i1)～i2)任一种方法：A sixth aspect of the present invention provides a computer device, the computer device comprising a memory and a processor, the memory storing a program, and the processor implementing any one of the following methods i1) to i2) when executing the program:
i1)本发明第四个方面的模型的构建方法；i1) A method for constructing a model according to the fourth aspect of the present invention;
i2)i2)
S1：获取受试样品中本发明第一个方面中的标志物的含量、活性和/或表达量；和S1: obtaining the content, activity and/or expression of the marker in the first aspect of the present invention in the test sample; and
S2：将S1获取的数据输入根据本发明第四个方面的构建方法构建的模型进行分析。S2: Input the data acquired in S1 into the model constructed according to the construction method of the fourth aspect of the present invention for analysis.
优选地，i2)中S1为获取受试样品中本发明第二个方面中的标志物组合的含量、活性和/或表达量。Preferably, S1 in i2) is to obtain the content, activity and/or expression level of the marker combination in the second aspect of the present invention in the test sample.
优选地，所述受试样品为本发明第一个方面中的受试样品。Preferably, the test sample is the test sample in the first aspect of the present invention.
优选地，i2)还包括如下步骤：根据得到的分析结果，输出信息。Preferably, i2) also includes the following step: outputting information according to the obtained analysis results.
本发明的第七个方面，提供一种计算机可存储介质，所述计算机可读存储介质包括存储的计算机程序；其中，在所述计算机程序运行时控制所述计算机可读存储介质实现本发明第六个方面中的i1)～i2)任一种方法。The seventh aspect of the present invention provides a computer-storable storage medium, wherein the computer-readable storage medium includes a stored computer program; wherein, when the computer program is running, the computer-readable storage medium is controlled to implement any one of methods i1) to i2) in the sixth aspect of the present invention.
本发明的第八个方面，提供一种构建结直肠癌模型的方法，调整所述模型中本发明第一个方面中标志物的含量、表达量和/或活性：The eighth aspect of the present invention provides a method for constructing a colorectal cancer model, wherein the content, expression and/or activity of the marker in the first aspect of the present invention in the model is adjusted:
当所述标志物在患有结直肠癌的待测对象中的含量、表达量和/或活性相对于未患有结直肠癌的待测对象(优选健康的待测对象)提高时，提高所述模型中所述标志物的含量、表达量和/或活性；When the content, expression level and/or activity of the marker in the test subject suffering from colorectal cancer is increased relative to that in the test subject not suffering from colorectal cancer (preferably a healthy test subject), increasing the content, expression level and/or activity of the marker in the model;
当所述标志物在患有结直肠癌的待测对象中的含量、表达量和/或活性相对于未患有结直肠癌的待测对象(优选健康的待测对象)降低时，降低所述模型中所述标志物的含量、表达量和/或活性。When the content, expression level and/or activity of the marker in the subject to be tested having colorectal cancer is reduced relative to the subject to be tested not having colorectal cancer (preferably a healthy subject to be tested), the content, expression level and/or activity of the marker in the model is reduced.
优选地，所述模型为动物模型。Preferably, the model is an animal model.
优选地，所述动物为大鼠、小鼠、或豚鼠。Preferably, the animal is a rat, a mouse, or a guinea pig.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
本发明的第九个方面，提供一种用于结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的方法，包含检测受试样品中本发明第一个方面中的标志物的含量、表达量和/或活性的步骤。The ninth aspect of the present invention provides a method for early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer, comprising the step of detecting the content, expression level and/or activity of the marker in the first aspect of the present invention in a test sample.
优选地，所述方法包含检测受试样品中本发明第二个方面中的标志物组合的含量、表达量和/或活性的步骤。Preferably, the method comprises the step of detecting the content, expression level and/or activity of the marker combination in the second aspect of the present invention in the test sample.
优选地，所述受试样品为本发明第一个方面中的受试样品。Preferably, the test sample is the test sample in the first aspect of the present invention.
优选地，采用本发明第一个方面中的产品检测受试样品中本发明第一个方面中的标志物的含量、表达量和/或活性。Preferably, the product of the first aspect of the present invention is used to detect the content, expression level and/or activity of the marker of the first aspect of the present invention in a test sample.
优选地，采用本发明第三个方面的产品检测受试样品中本发明第二个方面中的标志物组合的含量、表达量和/或活性。Preferably, the product of the third aspect of the present invention is used to detect the content, expression level and/or activity of the marker combination of the second aspect of the present invention in a test sample.
优选地，所述方法还包括如下步骤：将获取的受试样品中本发明第一个方面中的标志物或本发明第二个方面中的标志物组合的含量、表达量和/或活性的数据输入根据本发明第四个方面的构建方法构建的模型进行分析。Preferably, the method further comprises the step of inputting the data of the content, expression level and/or activity of the marker in the first aspect of the present invention or the combination of markers in the second aspect of the present invention in the test sample obtained into the model constructed according to the construction method of the fourth aspect of the present invention for analysis.
优选地，所述方法还包括如下步骤：根据得到的分析结果，输出信息。Preferably, the method further comprises the following step: outputting information according to the obtained analysis results.
优选地，所述结直肠癌包含结直肠癌早期(stageI和stageII)和/或结直肠癌晚期(stageIII和stageIV)。Preferably, the colorectal cancer includes early stage colorectal cancer (stage I and stage II) and/or late stage colorectal cancer (stage III and stage IV).
优选地，所述分期为区分结直肠癌早期(stageI和stageII)和结直肠癌晚期(stageIII和stageIV)。Preferably, the staging is to distinguish between early colorectal cancer (stage I and stage II) and late colorectal cancer (stage III and stage IV).
本发明的有益效果是：The beneficial effects of the present invention are:
本发明首次公开了ADAMTS8、ADGRE1、ADGRE2、ADGRE5、ADGRG2、AGR3、ANGPTL4、AREG、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CEACAM5、CFP、CKAP4、CLEC3B、CNTN1、CNTN4、CNTN5、COMP、CRTAC1、DCC、DLK1、EDA2R、ENPP6、ESM1、EXTL1、FAP、FASLG、FCER2、FCRL1、FGF21、GCG、GDF15、GNAS、GRK5、GSN、HMCN2、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGA11、ITGA2、ITGAM、ITGB1、ITGB7、ITIH3、ITM2A、KRT19、LBP、LMNB2、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PLXDC2、POF1B、PROK1、PTPRS、PTX3、RBFOX3、RET、SELL、SERPINA1、SOD3、SPON2、SPP1、TCL1A、THBS4、TMPRSS15、TNC、TNFRSF10B、TNFRSF11A、VSIG4中的一种或多种作为结直肠癌的早期筛查、诊断、分期、监测、疗效评估、或预后评估的标志物，通过检测上述标志物的含量、表达量和/或活性可以实现对结直肠癌的早期筛查、诊断、严重程度评估、监测、疗效评估、或预后评估。The present invention discloses for the first time ADAMTS8, ADGRE1, ADGRE2, ADGRE5, ADGRG2, AGR3, ANGPTL4, AREG, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CEACAM5, CFP, CKAP4, CLEC3B, CNTN1, CNTN4, CNTN5 , COMP, CRTAC1, DCC, DLK1, EDA2R, ENPP6, ESM1, EXTL1, FAP, FASLG, FCER2, FCRL1, FGF21, GCG, GDF15, GNAS, GRK5, GSN, HMCN2, IFNL1, IGDCC4, IGFBP1, IGSF3, IL4R, IL6 , ITGA11, ITGA2, ITGAM, ITGB1, ITGB7, ITIH3 、ITM2A、KRT19、LBP、LMNB2、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PLXDC2、POF1B、PROK1、PTPRS、PTX3、RBFOX3、RET、SELL , SERPINA1, SOD3, SPON2, SPP1, TCL1A, THBS4, TMPRSS15, TNC, TNFRSF10B, TNFRSF11A, VSIG4 as early screening, diagnosis, staging, monitoring, efficacy evaluation, or prognosis evaluation of colorectal cancer By detecting the content, expression and/or activity of the above markers, early screening, diagnosis, severity assessment, monitoring, efficacy assessment, or prognosis assessment of colorectal cancer can be achieved.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
图1是部分单marker的RandomForest模型和XGBboost模型的AUC比较的结果图。Figure 1 is a graph showing the AUC comparison between some single-marker RandomForest models and XGBboost models.
图2是部分2markers组合(TMPRSS15和GDF15；SPP1和ADGRE5)的ROC曲线图。FIG2 is a ROC curve diagram of some 2-markers combinations (TMPRSS15 and GDF15; SPP1 and ADGRE5).
图3是部分2markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。Figure 3 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 2markers combinations.
图4是部分3markers组合(SPP1、COMP和FCRL1；TMPRSS15、SPP1和SOD3；AREG、CEACAM5和PLXDC2)的ROC曲线图。FIG4 is a ROC curve diagram of some 3-markers combinations (SPP1, COMP and FCRL1; TMPRSS15, SPP1 and SOD3; AREG, CEACAM5 and PLXDC2).
图5是部分3markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。Figure 5 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 3markers combinations.
图6是部分4markers组合(SPP1、COMP、FCRL1和LMNB2；ADGRE1、GDF15、PTX3和THBS4)的ROC曲线图。FIG6 is a ROC curve diagram of some 4-markers combinations (SPP1, COMP, FCRL1 and LMNB2; ADGRE1, GDF15, PTX3 and THBS4).
图7是部分4markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。Figure 7 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 4-markers combinations.
图8是部分5markers组合(AREG、CEACAM5、PTX3、SPP1和PLXDC2；TMPRSS15、COMP、PTX3、PGA4和POF1B；SPP1、PLXDC2、SOD3、IL4R和BAG3；NOTCH1、COMP、GDF15、PTX3和PGA4)的ROC曲线图。Figure 8 is a ROC curve diagram of some 5-markers combinations (AREG, CEACAM5, PTX3, SPP1 and PLXDC2; TMPRSS15, COMP, PTX3, PGA4 and POF1B; SPP1, PLXDC2, SOD3, IL4R and BAG3; NOTCH1, COMP, GDF15, PTX3 and PGA4).
图9是部分5markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。Figure 9 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 5-markers combinations.
图10是部分6markers组合(SPP1、PLXDC2、SOD3、IL4R、BAG3和PROK1；AREG、CEACAM5、PTX3、CD48、CCL7和IGFBP1；NOTCH1、COMP、GDF15、PTX3、PGA4和CEACAM5)的ROC曲线图。Figure 10 is a ROC curve diagram of a partial 6-markers combination (SPP1, PLXDC2, SOD3, IL4R, BAG3 and PROK1; AREG, CEACAM5, PTX3, CD48, CCL7 and IGFBP1; NOTCH1, COMP, GDF15, PTX3, PGA4 and CEACAM5).
图11是部分6markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。FIG11 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 6-markers combinations.
图12是部分7markers组合(SPP1、COMP、LMNB2、PLXDC2、TCL1A、PROK1和ADGRG2；PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A和SOD3)的ROC曲线图。FIG12 is a ROC curve diagram of a partial 7-markers combination (SPP1, COMP, LMNB2, PLXDC2, TCL1A, PROK1 and ADGRG2; PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A and SOD3).
图13是部分7markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。FIG13 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 7-markers combinations.
图14是部分8markers组合(PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1和PCDH7；SPP1、LMNB2、SOD3、ADGRE5、PLXDC1、PROK1、LBP和FASLG)的ROC曲线图。FIG14 is a ROC curve diagram of a partial 8-markers combination (PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and PCDH7; SPP1, LMNB2, SOD3, ADGRE5, PLXDC1, PROK1, LBP and FASLG).
图15是部分8markers组合的RandomForest模型和XGBboost模型的AUC比较的结果图。FIG15 is a graph showing the AUC comparison between the RandomForest model and the XGBboost model for some 8-markers combinations.
具体实施方式DETAILED DESCRIPTION
以下通过具体的实施例对本发明的内容作进一步详细的说明。The present invention is further described in detail below through specific examples.
应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.
下列实施例中未注明具体条件的实验方法，通常按照常规条件，或按照制造厂商所建议的条件。本实施例中所使用的材料、试剂等，如无特别说明，为从商业途径得到的试剂和材料。The experimental methods in the following examples without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturers. The materials and reagents used in the examples are commercially available unless otherwise specified.
下列实施例中涉及的蛋白的信息如表1所示。The information of proteins involved in the following examples is shown in Table 1.
表1蛋白信息Table 1 Protein information
表1备注：Ensembl ID是Ensembl数据库中收录的基因检索ID；Uniprot ID是UniProt蛋白质数据中子库Swiss-Prot中收录的蛋白检索ID。Notes to Table 1: Ensembl ID is the gene search ID included in the Ensembl database; Uniprot ID is the protein search ID included in the Swiss-Prot sub-library of the UniProt protein database.
实施例1结直肠癌的诊断标志物Example 1 Diagnostic markers for colorectal cancer
1.临床样本收集1. Clinical Sample Collection
本实施例收集了院内139例诊断为结直肠癌患者、以及40例健康人作为对照的，收集在院术前的新鲜血液样本，通过蛋白检测邻位延伸技术PEA(Proximity ExtensionAssay)平台检测血液中的蛋白表达水平，作为用于建模预测的检测的标志物。根据患者疾病临床进展分型情况，将患者组分为两组：结直肠癌组139例，其中早期(stageI和stageII)60例、晚期(stageIII和stageIV)79例，健康人组40例。所有入组结直肠癌为新发疾病，且没有其他严重疾病及癌症，在采样时没有接受过手术或其他治疗手段。实验组中结直肠癌组的年龄范围是28～83岁，平均年龄是57.6岁，男女比例是85:54；对照组(健康人)中的年龄范围是22～77岁，平均年龄是51.5，男女比例是9:31。This embodiment collected 139 patients diagnosed with colorectal cancer in the hospital and 40 healthy people as controls, collected fresh blood samples before surgery in the hospital, and detected the protein expression level in the blood by the protein detection proximity extension technology PEA (Proximity Extension Assay) platform as a marker for modeling prediction. According to the clinical progression of the patient's disease, the patient group was divided into two groups: 139 cases in the colorectal cancer group, including 60 cases in the early stage (stage I and stage II), 79 cases in the late stage (stage III and stage IV), and 40 cases in the healthy group. All the colorectal cancers in the group were new diseases, and there were no other serious diseases and cancers. They had not received surgery or other treatments at the time of sampling. The age range of the colorectal cancer group in the experimental group was 28 to 83 years old, with an average age of 57.6 years old, and a male-female ratio of 85:54; the age range in the control group (healthy people) was 22 to 77 years old, with an average age of 51.5, and a male-female ratio of 9:31.
样本纳入准则：Sample inclusion criteria:
实验组纳入标准：(1)已确诊的术前结肠癌或直肠癌患者；(2)年龄在18～80岁，性别不限；(3)既往无其他部位恶性肿瘤史；(4)接受切除术前未接受任何其他形式的抗肿瘤治疗；(5)近三年没有输血历史。Inclusion criteria for the experimental group: (1) patients with confirmed preoperative colon or rectal cancer; (2) aged 18 to 80 years, regardless of gender; (3) no history of malignant tumors in other parts of the body; (4) no previous anti-tumor treatment before resection; (5) no history of blood transfusion in the past three years.
样本排除标准：(1)确诊的结直肠癌患者，但是已完成手术治疗，或者接受放疗、化疗和靶向药治疗；(2)其他非结直肠癌的肿瘤患者，或其他肿瘤结直肠转移的肿瘤患者。Sample exclusion criteria: (1) patients diagnosed with colorectal cancer but who have completed surgical treatment or received radiotherapy, chemotherapy, and targeted drug treatment; (2) patients with other non-colorectal cancer tumors or other tumors with colorectal metastasis.
临床表现：1)实验组，病理检测显示癌细胞存在，部分患者出现血便，结直肠区痉挛，贫血，表现虚弱和疲劳；2)对照组：健康人，没有肠不适等症状。Clinical manifestations: 1) Experimental group: pathological examination showed the presence of cancer cells, and some patients had bloody stools, colorectal cramps, anemia, weakness and fatigue; 2) Control group: healthy people, without symptoms such as intestinal discomfort.
在本实施例中，实验组及对照组是于2021年1月至2023年1月在中山大学附属第六附属医院就诊的患者，并严格按照上述纳入标准招募入组，共招募名139例诊断为结直肠癌患者以及40例健康人。所有标本采集均获得受试者家属签署的知情同意，并得到中山大学附属第六附属医院机构审查委员会批准。In this example, the experimental group and the control group were patients who were treated in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2021 to January 2023, and were recruited in strict accordance with the above inclusion criteria, with a total of 139 patients diagnosed with colorectal cancer and 40 healthy people recruited. All specimens were collected with the informed consent signed by the family members of the subjects and approved by the Institutional Review Board of the Sixth Affiliated Hospital of Sun Yat-sen University.
2.血样处理2. Blood Sample Processing
利用EDTA抗凝血紫头管采集入组患者及健康对照组的外周静脉血5mL，离心10分钟，取上层血浆，竖直放置-80℃冰箱保存。5 mL of peripheral venous blood was collected from the patients and the healthy control group using EDTA anticoagulant purple-headed tubes, centrifuged for 10 minutes, and the upper plasma was taken and stored vertically in a -80°C refrigerator.
3.蛋白质检测3. Protein Detection
本实施例中，发明人通过采用邻位延伸技术PEA(Proximity Extension Assay)平台对179例血浆样本进行血浆蛋白质组检测。具体在检测中，采用3072种蛋白特异性抗体各自与独特的PEA寡核苷酸探针进行单独标记，每种抗体都标记有两种独立且互补的序列，这些结合的抗体被混合成八个独立的384孔板，每个384孔板包括3个蛋白重复用于进行板间质量控制。在检测的过程中，179个样本被随机分布在3个不同的96孔板上，并与标记有PEA探针的抗体在+4℃下孵育过夜。免疫反应后，在室温下将延长和预扩增混合物加入到孵育的样本中进行PCR扩增。然后在加入个体样本索引序列前，将PCR扩增产物混合，然后进行第二次PCR扩增。样本混合后，对生成的文库进行磁珠纯化和Bioanalyzer上的质量控制。最后，使用Illumina的NovaSeq 6000仪器进行测序，使用两个S1流式细胞，读取长度为2×50碱基。已知的条形码序列的计数随后通过QC和标准化过程转化为归一化蛋白表达单位NPX，最后共定量2884个蛋白。In this embodiment, the inventors performed plasma proteome detection on 179 plasma samples by using the proximity extension technology PEA (Proximity Extension Assay) platform. Specifically, in the detection, 3072 protein-specific antibodies were individually labeled with unique PEA oligonucleotide probes, each antibody was labeled with two independent and complementary sequences, and these bound antibodies were mixed into eight independent 384-well plates, each 384-well plate including 3 protein repeats for inter-plate quality control. During the detection process, 179 samples were randomly distributed on 3 different 96-well plates and incubated overnight at +4°C with antibodies labeled with PEA probes. After the immune reaction, the extension and pre-amplification mixture was added to the incubated sample for PCR amplification at room temperature. Then, before adding the individual sample index sequence, the PCR amplification products were mixed, and then a second PCR amplification was performed. After the samples were mixed, the generated library was purified by magnetic beads and quality controlled on the Bioanalyzer. Finally, sequencing was performed using an Illumina NovaSeq 6000 instrument, using two S1 flow cells with a read length of 2 × 50 bases. The counts of known barcode sequences were then converted to normalized protein expression units (NPX) through a QC and normalization process, resulting in a total of 2884 proteins being quantified.
4.构建结直肠癌蛋白标志物筛查模型4. Construction of a colorectal cancer protein marker screening model
发明人利用XGBoost机器学习方法评估能够区分结直肠癌与健康人群的潜在蛋白。为了避免样本选择对机器学习建模的偏差，采用Bootstrap方法进行了100次随机建模。在每次建模中，选择139例结直肠癌样本和40例健康对照中的70％(125例)作为训练集，剩余30％(54例)作为测试集。The inventors used the XGBoost machine learning method to evaluate potential proteins that can distinguish colorectal cancer from healthy people. In order to avoid the bias of sample selection on machine learning modeling, 100 random modelings were performed using the Bootstrap method. In each modeling, 70% (125 cases) of 139 colorectal cancer samples and 40 healthy controls were selected as the training set, and the remaining 30% (54 cases) were used as the test set.
(1)对每个蛋白质的独立结直肠癌预测能力独立预测能力进行AUC(曲线下面积)、灵敏度和特异性评估，并计算了100次的均值及置信区间，对蛋白质的预测效力进行排序，筛选出AUC大于0.7的蛋白。(1) The independent colorectal cancer prediction ability of each protein was evaluated by AUC (area under the curve), sensitivity, and specificity. The mean and confidence interval were calculated 100 times. The predictive effectiveness of the proteins was ranked, and proteins with AUC greater than 0.7 were screened out.
(2)利用不限制蛋白数量的XGBoost机器学习算法建模，筛选出分类准确率高的模型，并统计了模型中各蛋白的权重和频率，从而确定了GDF15、PTX3、SPP1、TMPRSS15四个关键蛋白，用于预测模型构建。(2) The XGBoost machine learning algorithm with no restriction on the number of proteins was used to build the model, and the model with high classification accuracy was screened out. The weight and frequency of each protein in the model were statistically analyzed, thereby identifying four key proteins, GDF15, PTX3, SPP1, and TMPRSS15, for predictive model construction.
(3)在2884个蛋白中，利用XGBoost机器学习方法，评估了每个蛋白与GDF15、PTX3、SPP1或TMPRSS15中的一种的组合，进行了AUC、灵敏度和特异性评估，选择了AUC大于0.87的蛋白组合。(3) Among the 2884 proteins, the XGBoost machine learning method was used to evaluate the combination of each protein with one of GDF15, PTX3, SPP1, or TMPRSS15. The AUC, sensitivity, and specificity were evaluated, and protein combinations with an AUC greater than 0.87 were selected.
经过以上3步，把每一步得到的蛋白求并集，得到90个markers：ADAMTS8、ADGRE1、ADGRE2、ADGRE5、ADGRG2、AGR3、ANGPTL4、AREG、ASAH2、BAG3、BMP4、C9、CCL7、CD48、CDH23、CEACAM16、CEACAM5、CFP、CKAP4、CLEC3B、CNTN1、CNTN4、CNTN5、COMP、CRTAC1、DCC、DLK1、EDA2R、ENPP6、ESM1、EXTL1、FAP、FASLG、FCER2、FCRL1、FGF21、GCG、GDF15、GNAS、GRK5、GSN、HMCN2、IFNL1、IGDCC4、IGFBP1、IGSF3、IL4R、IL6、ITGA11、ITGA2、ITGAM、ITGB1、ITGB7、ITIH3、ITM2A、KRT19、LBP、LMNB2、LPL、MEGF9、MMP12、NOTCH1、NOTCH3、NOS2、NPY、NT5C1A、NTRK2、PCDH7、PGA4、PKD1、PLXDC1、PLXDC2、POF1B、PROK1、PTPRS、PTX3、RBFOX3、RET、SELL、SERPINA1、SOD3、SPON2、SPP1、TCL1A、THBS4、TMPRSS15、TNC、TNFRSF10B、TNFRSF11A、VSIG4；90个蛋白都具有显著性差异，具体如表2所示(其中，表2中：p.adj为t检验差异矫正P值，Mean_CRC为该蛋白在结直肠癌症中标准化之后的平均表达值，Mean_Healthy为该蛋白在健康对照人群中标准化之后的平均表达值，logFC为两组样本中平均表达值的差异倍数(当logFC大于0，表明该蛋白在结直肠癌患者中高表达；当logFC小于0，表明该蛋白在结直肠癌患者中低表达)，下同)；90个差异显著蛋白的AUC范围为：0.6107～0.8546。其中，61个蛋白质预测效力AUC大于0.7，具体如表3所示(其中，表3中Mean_AUC表示该蛋白组合在XGBoost机器学习模型中100次训练分类的平均AUC、sd_AUC为100次训练分类AUC的标准差、Median_AUC为100次训练分类AUC的中位值，下同)。可见，上述90个markers可用于诊断结直肠癌。After the above three steps, the proteins obtained in each step were combined to obtain 90 markers: ADAMTS8, ADGRE1, ADGRE2, ADGRE5, ADGRG2, AGR3, ANGPTL4, AREG, ASAH2, BAG3, BMP4, C9, CCL7, CD48, CDH23, CEACAM16, CEACAM5, CFP, CKAP4, CLEC3B, CNTN1, CNTN4, CNTN5, COMP, CRTAC1, DCC, DLK1, ED A2R, ENPP6, ESM1, EXTL1, FAP, FASLG, FCER2, FCRL1, FGF21, GCG, GDF15, GNAS, GRK5, GSN, HMCN2, IFNL1, IGDCC4, IGFBP1, IGSF3, IL4R, IL6, ITGA11, ITGA2, ITGAM, ITGB1, ITGB7, ITIH3, ITM2A, KRT19, LBP, LMNB2, LPL, MEGF9, MMP12, NOTCH1, NO TCH3, NOS2, NPY, NT5C1A, NTRK2, PCDH7, PGA4, PKD1, PLXDC1, PLXDC2, POF1B, PROK1, PTPRS, PTX3, RBFOX3, RET, SELL, SERPINA1, SOD3, SPON2, SPP1, TCL1A, THBS4, TMPRSS15, TNC, TNFRSF10B, TNFRSF11A, VSIG4; 90 proteins all had significant differences, as shown in Table 2 (Table 2 2: p.adj is the t-test difference correction P value, Mean_CRC is the average expression value of the protein after standardization in colorectal cancer, Mean_Healthy is the average expression value of the protein after standardization in the healthy control population, logFC is the difference multiple of the average expression value in the two groups of samples (when logFC is greater than 0, it indicates that the protein is highly expressed in colorectal cancer patients; when logFC is less than 0, it indicates that the protein is lowly expressed in colorectal cancer patients), the same below); the AUC range of 90 significantly different proteins is: 0.6107～0.8546. Among them, 61 proteins have a prediction efficiency AUC greater than 0.7, as shown in Table 3 (wherein, Mean_AUC in Table 3 represents the average AUC of 100 training classifications of the protein combination in the XGBoost machine learning model, sd_AUC is the standard deviation of the AUC of 100 training classifications, and Median_AUC is the median value of the AUC of 100 training classifications, the same below). It can be seen that the above 90 markers can be used to diagnose colorectal cancer.
表2训练集中存在显著性差异的90个蛋白Table 2 90 proteins with significant differences in the training set
表3测试集中预测效力AUC大于0.7的61个蛋白Table 3 61 proteins with prediction efficiency AUC greater than 0.7 in the test set
进一步的，为了验证上述选出的marker的准确性和稳定性，发明人利用RandoForest的机器学习方法，对上述选出性能较好的10个marker进行建模预测分析。建模方法如下：随机选择139例结直肠癌样本和40例健康对照中的70％(125例)作为训练集，剩余30％(54例)作为测试集。进行100次模型训练，然后统计100次模型的AUC的平均值和XGBboost的进行比较。结果如图1所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。Further, in order to verify the accuracy and stability of the above selected markers, the inventors used the machine learning method of RandoForest to model and predict the above selected 10 markers with better performance. The modeling method is as follows: 70% (125 cases) of 139 colorectal cancer samples and 40 healthy controls were randomly selected as training sets, and the remaining 30% (54 cases) were used as test sets. The model was trained 100 times, and then the average AUC of the 100 models was statistically compared with that of XGBboost. The results are shown in Figure 1: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
在上述的90个蛋白标志物中，组合marker实施例如下，分别用但不限于2个、3个，4个，5个、6个、7个、8个蛋白的组合，利用XGBoost机器学习方法对评估每种组合的AUC、灵敏度和特异性，并利用随机森林RandomForest机器学习方法对效果优异的组合进行进一步验证，具体如下：Among the above 90 protein markers, the combination marker examples are as follows, using but not limited to combinations of 2, 3, 4, 5, 6, 7, and 8 proteins, respectively, using the XGBoost machine learning method to evaluate the AUC, sensitivity, and specificity of each combination, and using the Random Forest RandomForest machine learning method to further verify the combination with excellent effects, as follows:
2markers组合：在90个markers中，排列组合所有的蛋白，共有90*89/2＝4005个组合，其预测效力AUC值的范围值为0.653～0.92，即上述4005个2markers组合可用于诊断结直肠癌；其中，ADGRE5、ADGRG2、AREG、CEACAM5、CLEC3B、CNTN5、COMP、EDA2R、ENPP6、EXTL1、FASLG、FCRL1、GDF15、HMCN2、ITGA11、ITGA2、ITGAM、ITGB7、KRT19、LMNB2、PLXDC1、PLXDC2、POF1B、PTX3、RET、SELL、SOD3、SPP1、THBS4、TMPRSS15这30个markers中的任意两个的组合，共435个组合，预测效力AUC值的范围值为0.79～0.92，其中427个组合AUC大于0.8，如表4所示，这组蛋白具有较高和较稳定的预测AUC。比如：TMPRSS15和GDF15；TMPRSS15和SPP1；TMPRSS15和KRT19等；部分2markers组合(TMPRSS15和GDF15；SPP1和ADGRE5)的ROC曲线如图2所示。2-marker combination: Among the 90 markers, all proteins are arranged and combined, with a total of 90*89/2=4005 combinations, and the range of the AUC value of the predictive effectiveness is 0.653-0.92, that is, the above 4005 2-marker combinations can be used to diagnose colorectal cancer; among them, ADGRE5, ADGRG2, AREG, CEACAM5, CLEC3B, CNTN5, COMP, EDA2R, ENPP6, EXTL1, FASLG, FCRL1, GDF15, HMC The combination of any two of the 30 markers N2, ITGA11, ITGA2, ITGAM, ITGB7, KRT19, LMNB2, PLXDC1, PLXDC2, POF1B, PTX3, RET, SELL, SOD3, SPP1, THBS4, and TMPRSS15, a total of 435 combinations, the prediction effectiveness AUC value range is 0.79-0.92, of which 427 combinations have an AUC greater than 0.8, as shown in Table 4. This group of proteins has a higher and more stable prediction AUC. For example: TMPRSS15 and GDF15; TMPRSS15 and SPP1; TMPRSS15 and KRT19, etc.; the ROC curves of some 2-marker combinations (TMPRSS15 and GDF15; SPP1 and ADGRE5) are shown in Figure 2.
在90个markers中2markers排列组合中(即上述4005个markers组合中除去上述435个markers组合)另外也有一些蛋白互补性较好的2markers组合，其AUC大于0.85，具体如表5所示，预测效力AUC值的范围值为0.85～0.92。表5所示的2markers组合可用于诊断结直肠癌。Among the 90 markers, there are also some 2-marker combinations with good protein complementarity (i.e., excluding the above 435 marker combinations from the above 4005 marker combinations), and their AUC is greater than 0.85, as shown in Table 5, and the range of the predictive effectiveness AUC value is 0.85 to 0.92. The 2-marker combination shown in Table 5 can be used to diagnose colorectal cancer.
同时单独验证了表6所示的2markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意两个的组合中的部分2markers组合)，结果如表6所示，预测效力AUC值的范围值为0.7458～0.8486。表6所示的2markers组合可用于诊断结直肠癌。At the same time, the 2-marker combination shown in Table 6 (part of the 2-marker combination in the combination of any two of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1) was verified separately, and the results are shown in Table 6. The range of the predictive efficacy AUC value is 0.7458-0.8486. The 2-marker combination shown in Table 6 can be used to diagnose colorectal cancer.
RandomRorest模型和XGBboost模型的AUC比较结果如图3所示：RandomRorest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomRorest model and the XGBboost model are shown in Figure 3: The AUC consistency of the RandomRorest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表4测试集中预测效力AUC大于等于0.8的2markers组合(30个蛋白中的任意两个的组合)Table 4 2-marker combinations with predictive efficacy AUC greater than or equal to 0.8 in the test set (combination of any two of the 30 proteins)
表5测试集中部分预测效力AUC大于等于0.85的2markers组合(上述4005个markers组合中除去上述435个markers组合)Table 5: Some 2-marker combinations with prediction effectiveness AUC greater than or equal to 0.85 in the test set (excluding the above 435 marker combinations from the above 4005 marker combinations)
表6测试集中部分预测效力AUC大于等于0.74的2markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意两个的组合中的部分2markers组合)Table 6 Some 2-marker combinations with prediction efficacy AUC greater than or equal to 0.74 in the test set (some 2-marker combinations in the combination of any two of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
3markers组合：90个marker排列组合成90*89*88/6＝117480个组合。比如：SPP1、COMP和FCRL1；TMPRSS15、SPP1和SOD3；PTX3、GDF15和THBS4等；这117480个3markers组合的预测效力AUC值的范围值为0.66～0.9543(由于组合过多，不一一列举3markers组合的AUC值，仅给出117480个3markers组合的AUC值的范围值，以展示上述117480个3markers组合的诊断效果)，平均AUC为0.8388。其中，表7中3markers组合的预测效力AUC值的范围值为0.92～0.9543，灵敏度的范围值为0.6856～0.9374，特异度的范围值为0.716～0.9842；其中，部分AUC大于等于0.92的3markers组合如表7所示(其中，表7中Mean_AUC表示该蛋白组合在XGBoost机器学习模型中100次训练分类的平均AUC、sd_AUC为100次训练分类AUC的标准差、Median_AUC为100次训练分类AUC的中位值、specificity为100次训练分类的平均特异性、sensitivity为100次训练分类的平均敏感度、accuracy为100次训练分类的平均正确率、ppv为阳性预测值和npv为阴性预测值，下同)，部分3markers组合(SPP1、COMP和FCRL1；TMPRSS15、SPP1和SOD3；AREG、CEACAM5和PLXDC2)的ROC曲线如图4所示。可见，上述117480个3markers组合可用于诊断结直肠癌。3-markers combination: 90 markers are arranged and combined into 90*89*88/6=117480 combinations. For example: SPP1, COMP and FCRL1; TMPRSS15, SPP1 and SOD3; PTX3, GDF15 and THBS4, etc.; the range of the predictive efficacy AUC values of these 117480 3-markers combinations is 0.66-0.9543 (due to too many combinations, the AUC values of the 3-markers combinations are not listed one by one, only the range of the AUC values of the 117480 3-markers combinations is given to show the diagnostic effect of the above 117480 3-markers combinations), and the average AUC is 0.8388. Among them, the range of the predictive effectiveness AUC values of the 3-marker combination in Table 7 is 0.92-0.9543, the range of the sensitivity is 0.6856-0.9374, and the range of the specificity is 0.716-0.9842; among them, some 3-marker combinations with AUC greater than or equal to 0.92 are shown in Table 7 (wherein, Mean_AUC in Table 7 represents the average AUC of the protein combination in 100 training classifications in the XGBoost machine learning model, sd_AUC is the standard deviation of the AUC of 100 training classifications, Median_AUC is the standard deviation of the AUC of 100 training classifications, and Median_AUC is the standard deviation of the AUC of 100 training classifications. UC is the median value of AUC of 100 training classifications, specificity is the average specificity of 100 training classifications, sensitivity is the average sensitivity of 100 training classifications, accuracy is the average correct rate of 100 training classifications, ppv is the positive predictive value and npv is the negative predictive value, the same below), and the ROC curves of some 3-marker combinations (SPP1, COMP and FCRL1; TMPRSS15, SPP1 and SOD3; AREG, CEACAM5 and PLXDC2) are shown in Figure 4. It can be seen that the above 117,480 3-marker combinations can be used to diagnose colorectal cancer.
同时单独验证了表8所示的3markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意三个的组合中的部分3markers组合)，结果如表8所示，预测效力AUC值的范围值为0.7458～0.8486。表8所示的3markers组合可用于诊断结直肠癌。At the same time, the 3-marker combination shown in Table 8 (part of the 3-marker combination in the combination of any three of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, and SERPINA1) was verified separately, and the results are shown in Table 8. The range of the predictive efficacy AUC value is 0.7458-0.8486. The 3-marker combination shown in Table 8 can be used to diagnose colorectal cancer.
RandomForest模型和XGBboost模型的AUC比较结果如图5所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomForest model and the XGBboost model are shown in Figure 5: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表7测试集中部分预测效力AUC大于等于0.92的3markers组合(上述117480个markers组合)Table 7 Some 3-marker combinations with prediction effectiveness AUC greater than or equal to 0.92 in the test set (the above 117480 marker combinations)
表8测试集中部分预测效力AUC大于等于0.77的3markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意三个的组合中的部分3markers组合)Table 8 Some 3-marker combinations with prediction efficacy AUC greater than or equal to 0.77 in the test set (some 3-marker combinations in the combination of any three of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
4markers组合：在3markers组合中AUC大于等于0.92的组合(622个组合，表7，即发明内容中的622个3markers组合)的基础上，与剩余的87个蛋白(即90个蛋白去除3markers组合中的3个蛋白)的组合，共622*(90-3)＝54114个组合，比如：ADGRE1、GDF15、PTX3和THBS4；PTX3、HMCN2、POF1B和FASLG；SPP1、COMP、FCRL1和LMNB2；等；这54114个4markers组合的预测效力AUC值的范围值为0.856～0.9687，其中，表9中4markers组合的预测效力AUC值的范围值为0.950～0.9687，灵敏度的范围值为0.7643～0.9477，特异度的范围值为0.7685～0.9817(由于组合过多，不一一列举4markers组合的AUC值，仅给出54114个4markers组合的AUC值的范围值，以展示上述54114个4markers组合的诊断效果)；其中，部分AUC大于等于0.95的4markers组合如表9所示，部分4markers组合(SPP1、COMP、FCRL1和LMNB2；ADGRE1、GDF15、PTX3和THBS4；)的ROC曲线如图6所示。可见，上述54114个4markers组合可用于诊断结直肠癌。4-markers combination: Based on the combinations with AUC greater than or equal to 0.92 in the 3-markers combination (622 combinations, Table 7, i.e., the 622 3-markers combinations in the content of the invention), and the remaining 87 proteins (i.e., 90 proteins minus 3 proteins in the 3-markers combination), a total of 622*(90-3)=54114 combinations, such as: ADGRE1, GDF15, PTX3 and THBS4; PTX3, HMCN2, POF1B and FASLG; SPP1, COMP, FCRL1 and LMNB2; etc.; The range of the predictive efficacy AUC values of these 54114 4-markers combinations is 0.856-0.9687, among which the 4-markers in Table 9 The range of the predictive efficacy AUC value of the rs combination is 0.950-0.9687, the range of the sensitivity is 0.7643-0.9477, and the range of the specificity is 0.7685-0.9817 (due to too many combinations, the AUC values of the 4-markers combination are not listed one by one, and only the range of the AUC values of 54114 4-markers combinations are given to show the diagnostic effect of the above 54114 4-markers combinations); among them, some 4-markers combinations with AUC greater than or equal to 0.95 are shown in Table 9, and the ROC curves of some 4-markers combinations (SPP1, COMP, FCRL1 and LMNB2; ADGRE1, GDF15, PTX3 and THBS4;) are shown in Figure 6. It can be seen that the above 54114 4-markers combinations can be used to diagnose colorectal cancer.
同时单独验证了表10所示的4markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意四个的组合中的部分4markers组合)，结果如表10所示，预测效力AUC值的范围值为0.8121～0.9494。表10所示的4markers组合可用于诊断结直肠癌。At the same time, the 4-marker combination shown in Table 10 (part of the 4-marker combination in the combination of any four of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, and SERPINA1) was verified separately, and the results are shown in Table 10. The range of the predictive efficacy AUC value is 0.8121 to 0.9494. The 4-marker combination shown in Table 10 can be used to diagnose colorectal cancer.
RandomForest模型和XGBboost模型的AUC比较结果如图7所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomForest model and the XGBboost model are shown in Figure 7: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表9测试集中部分预测效力AUC大于等于0.95的4markers组合(上述54114个4markers组合)Table 9 Some 4-marker combinations with prediction effectiveness AUC greater than or equal to 0.95 in the test set (the above 54114 4-marker combinations)
表10测试集中部分预测效力AUC大于等于0.81的4markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意四个的组合中的部分4markers组合)Table 10 Some 4-marker combinations with prediction efficacy AUC greater than or equal to 0.81 in the test set (some 4-marker combinations in the combination of any four of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
5markers组合：为了进一步验证每个蛋白是有效的，在4markers中AUC大于等于0.95的组合(332个组合，表9，即发明内容中的332个4markers组合)的基础上，和剩余的86个蛋白(即90个蛋白去除4markers组合中的4个蛋白)组合成332*(90-4)＝28552个组合。比如：AREG、CEACAM5、PTX3、SPP1和PLXDC2；TMPRSS15、COMP、PTX3、PGA4和POF1B；SPP1、PLXDC2、SOD3、IL4R和BAG3；NOTCH1、COMP、GDF15、PTX3和PGA4等；这28552个5markers组合的预测效力AUC值的范围值为0.93～0.9886，灵敏度的范围值为0.7465～0.9483，特异度的范围值为0.7683～0.9900(由于组合过多，不一一列举5markers组合的AUC值、灵敏度、特异度，仅给出28552个5markers组合的AUC值、灵敏度、特异度的范围值，以展示上述28552个5markers组合的诊断效果)；其中，部分AUC大于等于0.965的5markers组合如表11所示，部分5markers组合(AREG、CEACAM5、PTX3、SPP1和PLXDC2；TMPRSS15、COMP、PTX3、PGA4和POF1B；SPP1、PLXDC2、SOD3、IL4R和BAG3；NOTCH1、COMP、GDF15、PTX3和PGA4；)的ROC曲线如图8所示。可见，上述28552个5markers组合可用于诊断结直肠癌。5-markers combination: In order to further verify that each protein is effective, based on the combination of 4-markers with AUC greater than or equal to 0.95 (332 combinations, Table 9, i.e., 332 4-markers combinations in the content of the invention), the remaining 86 proteins (i.e., 90 proteins minus 4 proteins in the 4-markers combination) were combined into 332*(90-4)=28552 combinations. For example: AREG, CEACAM5, PTX3, SPP1 and PLXDC2; TMPRSS15, COMP, PTX3, PGA4 and POF1B; SPP1, PLXDC2, SOD3, IL4R and BAG3; NOTCH1, COMP, GDF15, PTX3 and PGA4, etc.; the predictive efficacy AUC values of these 28552 5-marker combinations range from 0.93 to 0.9886, the sensitivity ranges from 0.7465 to 0.9483, and the specificity ranges from 0.7683 to 0.9900 (due to too many combinations, the AUC values, sensitivity, and specificity of the 5-marker combinations are not listed one by one , only the range values of AUC values, sensitivity and specificity of 28552 5-marker combinations are given to demonstrate the diagnostic effect of the above 28552 5-marker combinations); among them, some 5-marker combinations with AUC greater than or equal to 0.965 are shown in Table 11, and the ROC curves of some 5-marker combinations (AREG, CEACAM5, PTX3, SPP1 and PLXDC2; TMPRSS15, COMP, PTX3, PGA4 and POF1B; SPP1, PLXDC2, SOD3, IL4R and BAG3; NOTCH1, COMP, GDF15, PTX3 and PGA4;) are shown in Figure 8. It can be seen that the above 28552 5-marker combinations can be used to diagnose colorectal cancer.
同时单独验证了表12所示的5markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意五个的组合中的部分5markers组合)，结果如表12所示，预测效力AUC值的范围值为0.8466～0.9648。表12所示的5markers组合可用于诊断结直肠癌。At the same time, the 5-marker combination shown in Table 12 (part of the 5-marker combination in any combination of five of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, and SERPINA1) was verified separately, and the results are shown in Table 12. The range of the predictive efficacy AUC value is 0.8466 to 0.9648. The 5-marker combination shown in Table 12 can be used to diagnose colorectal cancer.
RandomForest模型和XGBboost模型的AUC比较结果如图9所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomForest model and the XGBboost model are shown in Figure 9: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表11测试集中部分预测效力AUC大于等于0.965的5markers组合(上述28552个5markers组合)Table 11: Some 5-marker combinations with prediction effectiveness AUC greater than or equal to 0.965 in the test set (the above 28552 5-marker combinations)
表12测试集中部分预测效力AUC大于等于0.84的5markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意五个的组合中的部分5markers组合)Table 12: Some 5-marker combinations with prediction efficacy AUC greater than or equal to 0.84 in the test set (some 5-marker combinations in any combination of five of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
6markers组合：在5markers中AUC大于等于0.965的组合(486个组合)的基础上，在有4个蛋白重复的组合中，选择AUC最高的组合，剔除其他组合，剩余63个组合(表11中斜体的5markers组合，即发明内容中的63个5markers组合)，和剩余的85个蛋白(即90个蛋白去除5markers组合中的5个蛋白)组合成63*(90-5)＝5355个组合。比如SPP1、PLXDC2、SOD3、IL4R、BAG3和PROK1；AREG、CEACAM5、PTX3、CD48、CCL7和IGFBP1；NOTCH1、COMP、GDF15、PTX3、PGA4和CEACAM5等；这5355个6markers组合的预测效力AUC值的范围值为0.954～0.9836，灵敏度的范围值为0.801～0.964，特异度的范围值为0.809～0.989(由于组合过多，不一一列举6markers组合的AUC值、灵敏度、特异度，仅给出5355个6markers组合的AUC值、灵敏度、特异度的范围值，以展示上述5355个6markers组合的诊断效果)；其中，部分AUC大于等于0.975的6markers组合如表13所示，部分6markers组合(SPP1、PLXDC2、SOD3、IL4R、BAG3和PROK1；AREG、CEACAM5、PTX3、CD48、CCL7和IGFBP1；NOTCH1、COMP、GDF15、PTX3、PGA4和CEACAM5)的ROC曲线如图10所示。可见，上述5355个6markers组合可用于诊断结直肠癌。6-markers combination: Based on the combinations with AUC greater than or equal to 0.965 in 5-markers (486 combinations), among the combinations with 4 protein repeats, the combination with the highest AUC was selected, and other combinations were eliminated. The remaining 63 combinations (the 5-markers combinations in italics in Table 11, i.e., the 63 5-markers combinations in the content of the invention) and the remaining 85 proteins (i.e., 90 proteins minus 5 proteins in the 5-markers combination) were combined into 63*(90-5)=5355 combinations. For example, SPP1, PLXDC2, SOD3, IL4R, BAG3 and PROK1; AREG, CEACAM5, PTX3, CD48, CCL7 and IGFBP1; NOTCH1, COMP, GDF15, PTX3, PGA4 and CEACAM5; the predictive efficacy AUC values of these 5355 6-marker combinations range from 0.954 to 0.9836, the sensitivity ranges from 0.801 to 0.964, and the specificity ranges from 0.809 to 0.989 (due to too many combinations, the AUC values, sensitivity, and specificity of the 6-marker combinations are not listed one by one, only The range values of AUC values, sensitivity, and specificity of 5355 6-marker combinations are given to demonstrate the diagnostic effect of the above 5355 6-marker combinations); among them, some 6-marker combinations with AUC greater than or equal to 0.975 are shown in Table 13, and the ROC curves of some 6-marker combinations (SPP1, PLXDC2, SOD3, IL4R, BAG3, and PROK1; AREG, CEACAM5, PTX3, CD48, CCL7, and IGFBP1; NOTCH1, COMP, GDF15, PTX3, PGA4, and CEACAM5) are shown in Figure 10. It can be seen that the above 5355 6-marker combinations can be used to diagnose colorectal cancer.
同时单独验证了表14所示的6markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意六个的组合中的部分6markers组合)，结果如表14所示，预测效力AUC值的范围值为0.8832～0.9714。表14所示的6markers组合可用于诊断结直肠癌。At the same time, the 6-marker combination shown in Table 14 (part of the 6-marker combination in the combination of any six of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, and SERPINA1) was verified separately, and the results are shown in Table 14. The range of the predictive efficacy AUC value is 0.8832 to 0.9714. The 6-marker combination shown in Table 14 can be used to diagnose colorectal cancer.
RandomRorest模型和XGBboost模型的AUC比较结果如图11所示：RandomRorest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomRorest model and the XGBboost model are shown in Figure 11: the AUC consistency of the RandomRorest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表13测试集中部分预测效力AUC大于等于0.975的6markers组合(上述5355个6markers组合中)Table 13: Some 6-marker combinations with prediction effectiveness AUC greater than or equal to 0.975 in the test set (among the 5355 6-marker combinations mentioned above)
表14测试集中部分预测效力AUC大于等于0.88的6markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意六个的组合中的部分6markers组合)Table 14 Some 6-marker combinations with prediction efficacy AUC greater than or equal to 0.88 in the test set (some 6-marker combinations in any combination of six of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
7markers组合：在6markers中AUC大于等于0.975的组合(650个组合)的基础上，在有5个蛋白重复的组合中，选择AUC最高的组合，剔除其他组合，得到84个组合(表13中斜体的6markers组合，即发明内容中的84个6markers组合)，和剩余的84个蛋白组合成84*(90-6)＝7056个组合。比如SPP1、COMP、LMNB2、PLXDC2、TCL1A、PROK1和ADGRG2；PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A和SOD3等；这7056个7markers组合的预测效力AUC值的范围值为0.961～0.989，灵敏度的范围值为0.7113～0.96，特异度的范围值为0.7916～0.9868(由于组合过多，不一一列举7markers组合的AUC值、灵敏度、特异度，仅给出7056个7markers组合的AUC值、灵敏度、特异度的范围值，以展示上述7056个7markers组合的诊断效果)；其中，部分AUC大于等于0.987的7markers组合如表15所示，部分7markers组合(SPP1、COMP、LMNB2、PLXDC2、TCL1A、PROK1和ADGRG2；7-markers combination: Based on the combinations with AUC greater than or equal to 0.975 in 6-markers (650 combinations), in the combinations with 5 protein duplications, the combination with the highest AUC was selected, and other combinations were eliminated to obtain 84 combinations (the 6-markers combinations in italics in Table 13, i.e., the 84 6-markers combinations in the content of the invention), and the remaining 84 proteins were combined into 84*(90-6)=7056 combinations. For example, SPP1, COMP, LMNB2, PLXDC2, TCL1A, PROK1 and ADGRG2; PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A and SOD3; the range of predictive efficacy AUC values of these 7056 7-markers combinations is 0.961-0.989, the range of sensitivity is 0.7113-0.96, and the range of specificity is 0.7916-0.9868 (due to too many combinations, not listed one by one). The AUC values, sensitivity, and specificity of the 7-marker combinations are listed, and only the range values of the AUC values, sensitivity, and specificity of the 7056 7-marker combinations are given to demonstrate the diagnostic effect of the above 7056 7-marker combinations); among them, some 7-marker combinations with AUC greater than or equal to 0.987 are shown in Table 15, some 7-marker combinations (SPP1, COMP, LMNB2, PLXDC2, TCL1A, PROK1, and ADGRG2);
PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A和SOD3)的ROC曲线如图12所示。可见，上述7056个7markers组合可用于诊断结直肠癌。The ROC curves of 7 markers (PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A and SOD3) are shown in Figure 12. It can be seen that the above 7056 7 markers combination can be used to diagnose colorectal cancer.
同时单独验证了表16所示的7markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意七个的组合中的部分7markers组合)，结果如表16所示，预测效力AUC值的范围值为0.8884～0.9751。表16所示的7markers组合可用于诊断结直肠癌。At the same time, the 7 markers combination shown in Table 16 (part of the 7 markers combination in any combination of seven of the 11 protein markers, AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1) was verified separately, and the results are shown in Table 16. The range of the predictive efficacy AUC value is 0.8884 to 0.9751. The 7 markers combination shown in Table 16 can be used to diagnose colorectal cancer.
RandomForest模型和XGBboost模型的AUC比较结果如图13所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomForest model and the XGBboost model are shown in Figure 13: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表15测试集中部分预测效力AUC大于等于0.985的7markers组合(上述7056个7markers组合)Table 15: Some 7-marker combinations with prediction effectiveness AUC greater than or equal to 0.985 in the test set (the above 7056 7-marker combinations)
表16测试集中部分预测效力AUC大于等于0.88的7markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意七个的组合中的部分7markers组合)Table 16 Some 7-marker combinations with prediction efficacy AUC greater than or equal to 0.88 in the test set (some 7-marker combinations in any combination of seven of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
8markers组合：在7markers中AUC大于等于0.985的组合(40个组合，表15的7markers组合，即发明内容中的40个7markers组合)的基础上，和剩余的83个蛋白(即90个蛋白去除7markers组合中的7个蛋白)组合成40*(90-7)＝3320个组合。比如PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1和PCDH7；SPP1、LMNB2、SOD3、ADGRE5、PLXDC1、PROK1、LBP和FASLG等；这3320个8markers组合的预测效力AUC值的范围值为0.953～0.992，灵敏度的范围值为0.798～0.9685，特异度的范围值为0.8264～0.9855由于组合过多，不一一列举8markers组合的AUC值、灵敏度、特异度，仅给出3320个8markers组合的AUC值、灵敏度、特异度的范围值，以展示上述3403个8markers组合的诊断效果)；其中，部分AUC大于等于0.987的8markers组合如表17所示，部分8markers组合(PTX3、POF1B、THBS4、EXTL1、PGA4、ITM2A、PROK1和PCDH7；SPP1、LMNB2、SOD3、ADGRE5、PLXDC1、PROK1、LBP和FASLG)的ROC曲线如图14所示。可见，上述3320个8markers组合可用于诊断结直肠癌。8-markers combination: Based on the combinations with AUC greater than or equal to 0.985 in 7-markers (40 combinations, the 7-markers combinations in Table 15, i.e., the 40 7-markers combinations in the content of the invention), the remaining 83 proteins (i.e., 90 proteins minus 7 proteins in the 7-markers combination) are combined into 40*(90-7)=3320 combinations. For example, PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and PCDH7; SPP1, LMNB2, SOD3, ADGRE5, PLXDC1, PROK1, LBP and FASLG; the predictive efficacy AUC values of these 3320 8-marker combinations range from 0.953 to 0.992, the sensitivity ranges from 0.798 to 0.9685, and the specificity ranges from 0.8264 to 0.9855. Due to too many combinations, the AUC values, sensitivity, and specificity of the 8-marker combinations are not listed one by one. Only the range values of AUC values, sensitivity and specificity of 3320 8-marker combinations are given to demonstrate the diagnostic effect of the above 3403 8-marker combinations); among them, some 8-marker combinations with AUC greater than or equal to 0.987 are shown in Table 17, and the ROC curves of some 8-marker combinations (PTX3, POF1B, THBS4, EXTL1, PGA4, ITM2A, PROK1 and PCDH7; SPP1, LMNB2, SOD3, ADGRE5, PLXDC1, PROK1, LBP and FASLG) are shown in Figure 14. It can be seen that the above 3320 8-marker combinations can be used to diagnose colorectal cancer.
同时单独验证了表18所示的8markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意八个的组合中的部分8markers组合)，结果如表18所示，预测效力AUC值的范围值为0.9121～0.9740。表18所示的8markers组合可用于诊断结直肠癌。At the same time, the 8 markers combination shown in Table 18 (part of the 8 markers combination in any eight combinations of the 11 protein markers of AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1) was verified separately, and the results are shown in Table 18. The range of the predictive efficacy AUC value is 0.9121-0.9740. The 8 markers combination shown in Table 18 can be used to diagnose colorectal cancer.
RandomForest模型和XGBboost模型的AUC比较结果如图15所示：RandomForest模型和XGBboost模型的AUC一致性非常好：100次随机模型的平均AUC基本相当，且100次随机模型AUC的标准差SD(黑色线条)也很接近，即稳定性也很接近；表明实施列方案中模型算法的可替换性。The AUC comparison results of the RandomForest model and the XGBboost model are shown in Figure 15: The AUC consistency of the RandomForest model and the XGBboost model is very good: the average AUC of the 100 random models is basically the same, and the standard deviation SD (black line) of the AUC of the 100 random models is also very close, that is, the stability is also very close; indicating the interchangeability of the model algorithm in the implementation scheme.
表17测试集中部分预测效力AUC大于等于0.985的8markers组合(上述3320个8markers组合)Table 17: Some 8-marker combinations with prediction effectiveness AUC greater than or equal to 0.985 in the test set (the above 3320 8-marker combinations)
表18测试集中部分预测效力AUC大于等于0.91的8markers组合(AREG、CEACAM5、COMP、EDA2R、FCRL1、GDF15、PTX3、TMPRSS15、TNC、NOTCH1、SERPINA1这11个蛋白markers中的任意八个的组合中的部分8markers组合)Table 18 Partial prediction efficacy AUC of 8 markers combinations greater than or equal to 0.91 in the test set (partial 8 marker combinations in any eight combinations of the 11 protein markers AREG, CEACAM5, COMP, EDA2R, FCRL1, GDF15, PTX3, TMPRSS15, TNC, NOTCH1, SERPINA1)
本发明也可以采用流式荧光方法多联检测肿瘤标志物，通过采用免疫夹心多联检测法，分别用配对抗体中的一株抗体偶联微球，另一株抗体偶联发光物，检测一个对应的肿瘤标志物。然后，在同一反应容器中，用多指标配对抗体分别偶联微球和发光物，混合这些偶联抗体和样本，允许它们与目标抗原结合；通过流式细胞仪分析，可以根据微球的荧光和发光体的信号强度同时检测多个肿瘤标志物。接着，根据一系列正态分布的样本数据，采用统计方法确定不同置信水平下的参考区间。通过这样的流式免疫荧光多联检测技术，可以在临床诊断中提供快速、准确的多参数分析，从而对疾病进行更有效的监测和评估。The present invention can also use a flow fluorescence method to detect tumor markers in multiple ways. By using an immune sandwich multiple detection method, one of the paired antibodies is coupled to a microsphere, and the other antibody is coupled to a luminescent object to detect a corresponding tumor marker. Then, in the same reaction container, the microspheres and the luminescent object are coupled with multi-index paired antibodies, respectively, and these coupled antibodies and samples are mixed to allow them to bind to the target antigen; through flow cytometric analysis, multiple tumor markers can be detected simultaneously based on the fluorescence of the microspheres and the signal intensity of the luminescent object. Then, based on a series of normally distributed sample data, a statistical method is used to determine the reference interval at different confidence levels. Through such a flow immunofluorescence multiple detection technology, rapid and accurate multi-parameter analysis can be provided in clinical diagnosis, thereby more effectively monitoring and evaluating the disease.
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.
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| CN202410117025.3ACN118048455B (en) | 2024-01-26 | 2024-01-26 | Colorectal cancer marker and application thereof |
| PCT/CN2025/074312WO2025157220A1 (en) | 2024-01-26 | 2025-01-23 | Colorectal cancer marker and use thereof |
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