Alternative splicing events are prognostic in hepatocellular carcinoma.

Abstract

Alternative splicing events (ASEs) play a role in cancer development and progression. We investigated whether ASEs are prognostic for overall survival (OS) in hepatocellular carcinoma (HCC). RNA sequencing data was obtained for 343 patients included in The Cancer Genome Atlas. Matched splicing event data for these patients was then obtained from the TCGASpliceSeq database, which includes data for seven types of ASEs. Univariate and multivariate Cox regression analysis demonstrated that 3,814 OS-associated splicing events (OS-SEs) were correlated with OS. Prognostic indices were developed based on the most significant OS-SEs. The prognostic index based on all seven types of ASEs (PI-ALL) demonstrated superior efficacy in predicting OS of HCC patients at 2,000 days compared to those based on single ASE types. Patients were stratified into two risk groups (high and low) based on the median prognostic index. Kaplan-Meier survival analysis demonstrated that PI-ALL had the greatest capacity to distinguish between patients with favorable vs. poor outcomes. Finally, univariate Cox regression analysis demonstrated that the expression of 23 splicing factors was correlated with OS-SEs in the HCC cohort. Our data indicate that a prognostic index based on ASEs is prognostic for OS in HCC.