Alternative splicing (AS) contributes to protein diversity by modifying most gene transcriptions. Cancer generation and progression are associated with specific splicing events. However, AS signature in kidney renal clear cell carcinoma (KIRC) remains unknown. In this study, genome-wide AS profiles were generated in 537 patients with KIRC in the cancer genome atlas. With a total of 42 522 mRNA AS events in 10 600 genes acquired, 8164 AS events were significantly associated with the survival of patients with KIRC. Logistic regression analysis of the least absolute shrinkage and selection operator was conducted to identify an optimized multivariate prognostic predicting mode containing four predictors. In this model, the receptor-operator characteristic curves of the training set were built, and the areas under the curves (AUCs) at different times were >0.88, thus indicating a stable and powerful ability in distinguishing patients’ outcome. Similarly, the AUCs of the test set at different times were >0.73, verifying the results of the training set. Correlation and gene ontology analyses revealed some potential functions of prognostic AS events. This study provided an optimized survival-predicting model and promising data resources for future in-depth studies on AS mechanisms in KIRC.

Journal of cellular and molecular medicine. 2019 Sep 05 [Epub ahead of print]

Yongdi Zuo, Liang Zhang, Weihao Tang, Wanxin Tang

Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China., Chengdu Foreign Language School, Chengdu, China.