Title

Comprehensive analysis of alternative splicing in gastric cancer identifies epithelial-mesenchymal transition subtypes associated with survival.

Document Type

Article

Publication Date

12-13-2021

Publication Title

Cancer research

Keywords

JGM

JAX Source

Cancer Res 2021 Dec 13 [Online ahead of print]

ISSN

1538-7445

PMID

34903603

DOI

https://doi.org/10.1158/0008-5472.can-21-2117

Abstract

Alternatively spliced RNA isoforms are a hallmark of tumors, but their nature, prevalence, and clinical implications in gastric cancer have not been comprehensively characterized. We systematically profiled the splicing landscape of 83 gastric tumors and matched normal mucosa, identifying and experimentally validating eight splicing events that can classify all gastric cancers into three subtypes: epithelial-splicing, mesenchymal-splicing, and hybrid-splicing. These subtypes were associated with distinct molecular signatures and epithelial-mesenchymal transition markers. Subtype-specific splicing events were enriched in motifs for splicing factors RBM24 and ESRP1, which were upregulated in mesenchymal-splicing and epithelial-splicing tumors, respectively. A simple classifier based only on RNA levels of RBM24 and ESRP1, which can be readily implemented in the clinic, was sufficient to distinguish gastric cancer subtypes and predict patient survival in multiple independent patient cohorts. Overall, this study provides insights into alternative splicing in gastric cancer and the potential clinical utility of splicing-based patient classification.

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