Abstract 1583: The interaction of stromal components and tumor cells dictates the tumor progression and clinical outcomes in stomach cancer

Abstract

Abstract A subset of gastric cancers (GC) show activated epithelial-to-mesenchymal transformation (EMT), but it is of debate as to the origins of the EMT signals (i.e., from tumor cells or microenvironments) and how they are associated with clinical outcomes. In this study, we observed that mesenchymal GCs comprising 30-40% of datasets showed elevated level of infiltrating stromal cells and worse clinical outcomes. The analysis of xenograft sequencing revealed that the transcriptional signals representing EMT mainly come from stromal cells instead of tumor cells. In addition, no evidence of tumor-originating, EMT-driven stromal cells was found in single cell RNA sequencing data. Interestingly, expression of EMT signature genes in primary tumor was highly correlated with that of mouse genes. Microenvironment profiling identified a specific T cell subtypes associated with mesenchymal GCs such as T cell gamma-delta. Finally, deconvolution-based tumor, immune and stromal cells in mesenchymal GCs showed the YAP1 activation, representing the consequences of interactions of stromal component and cancer as well as defining the intrinsic and extrinsic hallmarks of mesenchymal GCs. Citation Format: Seungho Lee, Taemin Kim, Jaeho Cheong, Hyongbum Kim, Sunghwan Lee. The interaction of stromal components and tumor cells dictates the tumor progression and clinical outcomes in stomach cancer [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 1583.