Alternative Splicing Events and Splicing Factors Are Prognostic in Adrenocortical Carcinoma

Front Genet. 2020 Sep 3:11:918. doi: 10.3389/fgene.2020.00918. eCollection 2020.

Abstract

Alternative splicing is involved in the pathogenesis of human diseases, including cancer. Here, we investigated the potential application of alternative splicing events (ASEs) and splicing factors (SFs) in the prognosis of adrenocortical carcinoma (ACC). Transcriptome data from 79 ACC cases were downloaded from The Cancer Genome Atlas database, and percent spliced-in values of seven splicing types were downloaded from The Cancer Genome Atlas SpliceSeq database. By the univariate Cox regression analysis, 1,839 survival-related ASEs were identified. Prognostic indices based on seven types of survival-related ASEs were calculated by multivariate Cox regression analysis. Survival curves and receiver operating characteristic curves were used to assess the diagnostic value of the prognostic model. Independent prognosis analysis identified several ASEs (e.g., THNSL2| 54469| ME) that could be used as biomarkers to predict the prognosis of patients with ACC accurately. By analyzing the co-expression correlation between SFs and ASEs, 188 highly correlated interactions were established. From the protein interaction network, we finally screened six hub SFs, including YBX1, SART1, PRCC, SNRPG, SNRPE, and SF3B4, whose expression levels were significantly related to the overall survival and prognosis of ACC. Our findings provide a reliable model for predicting the prognosis of ACC patients based on aberrant alternative splicing patterns.

Keywords: Adrenocortical carcinoma; alternative splicing; hub gene; prognosis; splicing factor.