Abstract 5726: Splicing-based classifier for gastric cancer identifies epithelial-mesenchymal transition subtypes associated with survival

Abstract

Abstract Alternatively spliced RNA isoforms are a hallmark of tumors, but their nature, prevalence, and clinical implications in gastric cancer are unknown. We systematically profiled the splicing landscape of 83 gastric tumors and matched normal mucosa. We identified and experimentally validated 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, and which is thus readily implementable in the clinic, is sufficient to distinguish gastric cancer subtypes and predict patient survival in multiple independent patient cohorts Citation Format: Yukyung Jun, Yun-Suhk Suh, SungHee Park, Jieun Lee, Jong-Il Kim, Sanghyuk Lee, Wan-Ping Lee, Olga Anczuków, Han-Kwang Yang, Charles Lee. Splicing-based classifier for gastric cancer identifies epithelial-mesenchymal transition subtypes associated with survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5726.