The identification of alternative polyadenylation in stomach adenocarcinomas using the genotype-tissue expression project and the cancer genome atlas– stomach adenocarcinoma profiles

Abstract

Objective: Alternative polyadenylation (APA) is a common mechanism that is present in most human genes and determines the length of the messenger ribonucleic acid (mRNA) three prime untranslated region (3ʹ-UTR), which can give rise to changes in mRNA stability and localization. However, little is known about the specific changes related to APA in stomach adenocarcinomas (STADs). Methods: We integrated RNA sequencing data from The Cancer Genome Atlas and Genotype-Tissue Expression project to comprehensively analyze APA events in 289 cases of STAD. Results: Our results showed that APA events were widespread in patients with STAD and were rich in genes related to known STAD pathways. The APA events result in the loss of tumor-suppressing micro-ribonucleic acid (miRNA) binding sites and increased heterogeneity in the length of the 3ʹ-UTR altered genes. Survival analysis revealed that specific subsets of 3ʹ-UTR-altered genes independently characterized a poor prognostic cohort among patients with STAD, thereby indicating the potential of APA as a new prognostic biomarker. Conclusion: Our single-cancer analysis showed that by losing miRNA regulation, APA can become a driving factor for regulating the expression of oncogenic genes in STAD and promote its development. Our research revealed that APA events regulated STAD genes that were functionally related, thereby providing a new approach for gaining a better understanding of the progress of STADs and a means for identifying new drug targets as avenues of treatment.