Integrative bioinformatics analysis of prognostic alternative splicing signatures in gastric cancer

Background: The potential prognostic value of alternative splicing (AS) variants and regulatory splicing factors in gastric carcinogenesis is unclear. We aimed to exploit the aberrant AS signatures and splicing factors involved in gastric cancer (GC) and to determine their prognostic predictive values. Methods: We performed detailed data acquisition using the Cancer Genome Atlas project and profiled genome-wide AS signatures in a cohort of 190 patients with stomach adenocarcinoma (STAD). Prognostic prediction models and splicing correlation networks were assessed using an integrative bioinformatics analysis approach. Results: We detected 1,308 overall survival (OS)-related AS signatures in 993 genes, most of which were favorable prognostic factors. Six splicing factors have been suggested to be dysregulated in GC, i.e., DHX15, PPP4R2, PRPF3813, R13M9, RBM15, and 11.F3. Another notable finding was that most favorable prognosis AS events were positively correlated with expression of splicing factors, while a majority of poor survival prognostic AS genes were negatively associated with the expression of splicing factors. Conclusions: To our kiowledge, the current study provided the first comprehensive profiling of global modifications in the RNA splicing to identify survival associated AS signatures of GC specific genes. Our findings contribute to a better understanding of aberrant AS signatures and splicing factors in STAD, which can potentially be used as prognostic biomarkers and therapeutic targets for GC.