Comprehensive Analysis of Alternative Splicing in Gastric Cancer Identifies Epithelial-Mesenchymal Transition Subtypes Associated with Survival

Yukyung Jun, Yun Suhk Suh, Sunghee Park, Jieun Lee, Jong Il Kim, Sanghyuk Lee, Wan Ping Lee, Olga Anczukow, Han Kwang Yang, Charles Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 (EpiS), mesenchymal-splicing (MesS), 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 MesS and EpiS 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 splicingbased patient classification. Significance: This study presents a comprehensive analysis of alternative splicing in the context of patient classification, molecular mechanisms, and prognosis in gastric cancer.

Original languageEnglish
Pages (from-to)543-555
Number of pages13
JournalCancer Research
Volume82
Issue number4
DOIs
StatePublished - 15 Feb 2022

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