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

Authors

Yukyung Jun, The Jackson LaboratoryFollow
Yun-Suhk Suh
SungHee Park, The Jackson LaboratoryFollow
Jieun Lee
Jong-Il Kim
Sanghyuk Lee
Wan-Ping Lee, The Jackson LaboratoryFollow
Olga Anczuków, The Jackson LaboratoryFollow
Han-Kwang Yang
Charles Lee, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

2-15-2022

Publication Title

Cancer research

Keywords

JGM, Adult, Aged, Aged, 80 and over, Alternative Splicing, Cell Line, Tumor, Cluster Analysis, Epithelial-Mesenchymal Transition, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meier Estimate, Male, Middle Aged, RNA Splicing Factors, RNA-Binding Proteins, RNA-Seq, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms

JAX Source

Cancer Res 2022 Feb 15; 82(4):543-555.

Volume

82

Issue

4

First Page

543

Last Page

555

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 (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 splicing-based 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.

Comments

This open access article is distributed under Creative Commons Attribution- NonCommercial-NoDerivatives License 4.0 International.

Recommended Citation

Jun Y, Suh Y, Park S, Lee J, Kim J, Lee S, Lee W, Anczuków O, Yang H, Lee C. Comprehensive Analysis of Alternative Splicing in Gastric Cancer Identifies Epithelial-Mesenchymal Transition Subtypes Associated with Survival. Cancer Res 2022 Feb 15; 82(4):543-555.