The landscape of alternative splicing reveals novel events associated with tumorigenesis and the immune microenvironment in gastric cancer

Abstract

Alternative splicing (AS), contributing to vast protein diversity from a rather limited number of genes in eukaryotic transcripts, has emerged as an important signature for tumor initiation and progression. However, a systematic understanding of its functional impact and relevance to gastric cancer (GC) tumorigenesis is lacking. Differentially expressed AS (DEAS) was verified among GC-associated AS events based on RNA-seq profiles from the TCGA database. Functional enrichment analysis, unsupervised clustering analysis and prognostic models were used to infer the potential roles of DEAS events and their molecular, clinical and immune features. In total, 12,225 AS events were detected from 5,199 genes, among which 314 AS events were identified as DEAS events in GC. The parental genes of the DEAS events were significantly enriched in the regulation of GC-related processes. The splicing correlation network suggested a significant relationship between DEAS events and splicing factors (SFs). Three clusters of DEAS events were identified to be different in prognosis, cancer-specific signatures and immune features between distinct clusters. Univariate and multivariate analyses regarded 3 DEAS events as independent prognostic indicators. Profiling of the AS landscape in GC elucidated the functional roles of the splicing network in GC and might serve as a novel prognostic indicator and therapeutic target.