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. 2018 Apr 19;9(10):1754-1764.
doi: 10.7150/jca.24569. eCollection 2018.

Alternative splicing events implicated in carcinogenesis and prognosis of colorectal cancer

Jingwei Liu  1 , Hao Li  1 , Shixuan Shen  1 , Liping Sun  1 , Yuan Yuan  1 , Chengzhong Xing  1
Affiliations

Alternative splicing events implicated in carcinogenesis and prognosis of colorectal cancer

Jingwei Liu et al. J Cancer. .

Abstract

Background: Emerging evidence suggested that aberrant alternative splicing (AS) is pervasive event in development and progression of cancer. However, the information of aberrant splicing events involved in colorectal carcinogenesis and progression is still elusive. Materials and Methods: In this study, splicing data of 499 colon adenocarcinoma cases (COAD) and 176 rectum adenocarcinoma (READ) with clinicopathological information were obtained from The Cancer Genome Atlas (TCGA) to explore the changes of alternative splicing events in relation to the carcinogenesis and prognosis of colorectal cancer (CRC). Gene interaction network construction, functional and pathway enrichment analysis were performed by multiple bioinformatics tools. Results: Overall, most AS patterns were more active in CRC tissues than adjacent normal ones. We detected altogether 35391 AS events of 9084 genes in COAD and 34900 AS events of 9032 genes in READ, some of which were differentially spliced between cancer tissues and normal tissues including genes of SULT1A2, CALD1, DTNA, COL12A1 and TTLL12. Differentially spliced genes were enriched in biological process including muscle organ development, cytoskeleton organization, actin cytoskeleton organization, biological adhesion, and cell adhesion. The integrated predictor model of COAD showed an AUC of 0.805 (sensitivity: 0.734; specificity: 0.756) while READ predictor had an AUC of 0.738 (sensitivity: 0.614; specificity: 0.900). In addition, a number of prognosis-associated AS events were discovered, including genes of PSMD2, NOL8, ALDH4A1, SLC10A7 and PPAT. Conclusion: We draw comprehensive profiles of alternative splicing events in the carcinogenesis and prognosis of CRC. The interaction network and functional connections were constructed to elucidate the underlying mechanisms of alternative splicing in CRC.

Keywords: alternative splicing; carcinogenesis; colorectal cancer; prognosis..

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Representative model of seven different alternative splicing types.
Figure 2
Figure 2
Upset plot of different types of alternative splicing types. (A), COAD; (B), READ.
Figure 2
Figure 2
Upset plot of different types of alternative splicing types. (A), COAD; (B), READ.
Figure 3
Figure 3
Difference of alternative splicing in CRC tissues and normal ones. (A), COAD; (B), READ.
Figure 4
Figure 4
Functional enrichment analysis results of differentially spliced genes in CRC. (A), gene-gene interaction network; (B), GO analysis and KEGG analysis.
Figure 4
Figure 4
Functional enrichment analysis results of differentially spliced genes in CRC. (A), gene-gene interaction network; (B), GO analysis and KEGG analysis.
Figure 5
Figure 5
ROC curve evaluating the potential of alternative splicing in prediction of COAD risk. (A), different alternative splicing types; (B), integrated predictor.
Figure 6
Figure 6
Representative survival-associated alternative splicing events in COAD. (A), AD of PSMD2; (B) AA of NOL8; (C), AA of PPAT; (D), AA of PIGH.
See this image and copyright information in PMC

References

    1. Anczukow O, Krainer AR. Splicing-factor alterations in cancers. RNA (New York, NY) 2016;22(9):1285–1301. - PMC - PubMed
    1. Bates DO, Morris JC, Oltean S, Donaldson LF. Pharmacology of Modulators of Alternative Splicing. Pharmacological reviews. 2017;69(1):63–79. - PMC - PubMed
    1. Donaldson LF, Beazley-Long N. Alternative RNA splicing: contribution to pain and potential therapeutic strategy. Drug discovery today. 2016;21(11):1787–1798. - PMC - PubMed
    1. Kozlovski I, Siegfried Z, Amar-Schwartz A, Karni R. The role of RNA alternative splicing in regulating cancer metabolism. Human genetics. 2017;136(9):1113–1127. - PubMed
    1. Lee SC, Abdel-Wahab O. Therapeutic targeting of splicing in cancer. Nature medicine. 2016;22(9):976–986. - PMC - PubMed