AS-CMC: a pan-cancer database of alternative splicing for molecular classification of cancer

Abstract

Alternative splicing (AS) is a post-transcriptional regulation that leads to the complexity of the transcriptome. Despite the growing importance of AS in cancer research, the role of AS has not been systematically studied, especially in understanding cancer molecular classification. Herein, we analyzed the molecular subtype-specific regulation of AS using The Cancer Genome Atlas data and constructed a web-based database, named Alternative Splicing for Cancer Molecular Classification (AS-CMC). Our system harbors three analysis modules for exploring subtype-specific AS events, evaluating their phenotype association, and performing pan-cancer comparison. The number of subtype- specific AS events was found to be diverse across cancer types, and some differentially regulated AS events were recurrently found in multiple cancer types. We analyzed a subtype-specific AS in exon 11 of mitogen-activated protein kinase kinase 7 (MAP3K7) as an example of a pan-cancer AS biomarker. This AS marker showed significant association with the survival of patients with stomach adenocarcinoma. Our analysis revealed AS as an important determinant for cancer molecular classification. AS-CMC is the first web-based resource that provides a comprehensive tool to explore the biological implications of AS events, facilitating the discovery of novel AS biomarkers.