Movatterモバイル変換


[0]ホーム

URL:


Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Free PMC article
Full text links

Actions

Share

.2020 Aug;20(2):1866-1878.
doi: 10.3892/ol.2020.11695. Epub 2020 Jun 5.

Wide-ranging analysis of survival-related alternative splicing events in invasive breast carcinoma

Affiliations

Wide-ranging analysis of survival-related alternative splicing events in invasive breast carcinoma

Keren Jia et al. Oncol Lett.2020 Aug.

Abstract

Invasive breast carcinoma (BRCA) is a serious disease that threatens the survival time of those affected. Alternative splicing (AS) involved in BRCA pathogenesis may be a potential therapeutic target. However, to the best of our knowledge, a systematic analysis of survival-related alternative splicing events (SREs) has not yet been reported. The aim of the present study was to identify SREs and analyze their potential biological functions as BRCA prognostic biomarkers. An UpSet plot demonstrated AS global characteristics. Cox's proportional hazards regression model quantitatively demonstrated the prognostic relevance of AS events. Functional enrichment analysis investigated the potential pathways through which AS events affect BRCA progression. The receiver operating characteristic curve model determined the clinical significance of AS events represented using percent-spliced-in (PSI) values. The regulatory network of splicing factors (SFs) and AS events laid the foundation for studying the role of SFs in BRCA. The present study identified 1,215 SREs and their distribution characteristics, suggesting that AS events in exon skipping (ES) primarily exerted normal physiological functions, while AS events in alternative terminator sites had the most significant prognostic effect. The present study demonstrated that survival-associated genes are involved primarily in certain biological processes of ribosomal proteins. In the diagnostic model, the alternative acceptor site, alternative donor site, alternative promoter site and ES performed well. ELAVL4 was the key gene associated with prognosis and SREs. In conclusion, a number of AS events affect BRCA initiation, progression and prognosis. The PSI value of AS events has the potential to diagnose BRCA and predict a prognosis; however, this must be confirmed in additional studies.

Keywords: alternative splicing; invasive breast carcinoma; prognosis; splicing factor.

Copyright: © Jia et al.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
A total of seven alternative splicing types. Each rectangle represents a part of pre-mRNAs. The two rectangles connected by lines indicate that the corresponding two sequences are joined together after alternative splicing.
Figure 2.
Figure 2.
Distribution of SREs and related genes in invasive breast carcinoma. The y-axis is AS type. The x-axis is the number of cases. (A) Green strips represent the number of AS events. Blue strips represent the number of AS event-associated genes. (B) Green strips represent the number of SREs. Blue strips represent the number of SRGs. AS, alternative splicing; SRE, survival-related alternative splicing event; SRG, survival-related gene; BRCA, breast carcinoma; RI, retained intron; ME, mutually exclusive exons; ES, exon skipping; AT, alternative terminator; AP, alternative promoter; AD, alternative donor site; AA, alternative acceptor site.
Figure 3.
Figure 3.
UpSet plot for all AS events. Blue strip shows the number of events included in each AS type. Dots and lines represent subsets of AS events. The AS types corresponding to the dots are contained in the subtype. The histogram represents the number of genes in each subset. (A) All genes. (B) Survival-related genes. AS, alternative splicing; RI, retained intron; ME, mutually exclusive exons; ES, exon skipping; AT, alternative terminator; AP, alternative promoter; AD, alternative donor site; AA, alternative acceptor site.
Figure 4.
Figure 4.
Survival curve for the weighted percent-spliced-in value. Red and blue lines represent changes in survival probability in days in the group with lower and higher values, respectively. Red and blue areas represent the 95% confidence interval. The number of individuals in a group who remain alive at a certain point in time is the number at risk, which was exhibited in the lower part of each plot. (A) The AA type, (B) AD type, (C) AP type, (D) AT type, (E) ES type and (F) ME type. (G) RI type, (H) based on the 10 most significant SREs. (I) Third-level transcriptome data for ELAVL4. AA, alternative acceptor; AD, alternative donor; AP, alternative promoter; AT, alternative promoter; ES, exon skipping; ME, mutually exclusive exon; RI, retained intron; SRE, alternative splicing event.
Figure 4.
Figure 4.
Survival curve for the weighted percent-spliced-in value. Red and blue lines represent changes in survival probability in days in the group with lower and higher values, respectively. Red and blue areas represent the 95% confidence interval. The number of individuals in a group who remain alive at a certain point in time is the number at risk, which was exhibited in the lower part of each plot. (A) The AA type, (B) AD type, (C) AP type, (D) AT type, (E) ES type and (F) ME type. (G) RI type, (H) based on the 10 most significant SREs. (I) Third-level transcriptome data for ELAVL4. AA, alternative acceptor; AD, alternative donor; AP, alternative promoter; AT, alternative promoter; ES, exon skipping; ME, mutually exclusive exon; RI, retained intron; SRE, alternative splicing event.
Figure 5.
Figure 5.
ROC curves for 5-year survival and diagnostic models. The ROC curves present the sensitivity and (1-specificity) values for indicators at different cutoff values. (A) The 5-year survival model. (B) Diagnostic model. ROC, receiver operating characteristic; RI, retained intron; ME, mutually exclusive exons; ES, exon skipping; AT, alternative terminator; AP, alternative promoter; AD, alternative donor site; AA, alternative acceptor site. TOP10, 10 SREs with the smallest P-values.
Figure 6.
Figure 6.
Protein-protein interaction network for survival-associated genes. Color intensity represents the number of nodes connected to one node. Thick and thin lines represent strong and weak co-expression associations, respectively.
Figure 7.
Figure 7.
Regulatory network for SFs and alternative splicing events. The green node represents the survival-related SF, named ELAVL4. Red and blue nodes represent SREs that increase and decrease risk, respectively. Purple and orange lines represent the positive and negative correlations of connected nodes, respectively. Thick lines indicate a strong correlation, thin lines indicate a weak correlation. SRE, alternative splicing events; SF, splicing factor; HR, hazard ratio.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Miao H, Verkooijen HM, Chia KS, Bouchardy C, Pukkala E, Larønningen S, Mellemkjær L, Czene K, Hartman M. Incidence and outcome of male breast cancer: An international population-based study. J Clin Oncol. 2011;29:4381–4386. doi: 10.1200/JCO.2011.36.8902. - DOI - PubMed
    1. Coughlin SS. Social determinants of breast cancer risk, stage, and survival. Breast Cancer Res Treat. 2019;177:537–548. doi: 10.1007/s10549-019-05340-7. - DOI - PubMed
    1. San Miguel Y, Gomez SL, Murphy JD, Schwab RB, McDaniels-Davidson C, Canchola AJ, Molinolo AA, Nodora JN, Martinez ME. Age-related differences in breast cancer mortality according to race/ethnicity, insurance, and socioeconomic status. BMC Cancer. 2020;20:228. doi: 10.1186/s12885-020-6696-8. - DOI - PMC - PubMed
    1. DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–448. doi: 10.3322/caac.21412. - DOI - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34. doi: 10.3322/caac.21551. - DOI - PubMed

Related information

LinkOut - more resources

Full text links
Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.


[8]ページ先頭

©2009-2025 Movatter.jp