Transcriptome-wide analysis of alternative mRNA splicing signature in the diagnosis and prognosis of stomach adenocarcinoma

Abstract

Alternative mRNA splicing (AS) contributes greatly to expanding the diversity and function of the proteome. Increasing evidence has suggested that dysregulation of mRNA splicing may be associated with various types of cancer. In the present study, RNA sequencing data were used to investigate alterations to the global mRNA splicing landscape of cellular genes from 452 stomach adenocarcinoma (STAD) tissues available in The Cancer Genome Atlas. Seven types of AS events, including the profiles of exon skipping events, were analyzed using SpliceSeq software. A total of 60,754 AS events in 10,611 genes were detected, more than half of which were exon skipping events. The AS events were compared between 415 STAD tissues and 37 normal tissues, and 3,895 differentially spliced cancer-specific events were identified. In addition, the association of the AS events with the overall survival of 373 STAD patients was analyzed. Multivariate Cox regression analysis revealed that prognosis prediction models based on the AS events with clinical parameters had an excellent performance in predicting the survival of STAD patients. This study provides a comprehensive portrait of global changes in mRNA splicing signatures that occur in gastric cancer. These results allowed the identification of a core set of AS in gastric cancer and indicated that AS events may serve as prognostic indicators.