Abstract 151: Comprehensive characterization of gastric cancer at single-cell resolution

Abstract

Abstract The gastric carcinoma cells have complex interactions with diverse cell types in the associated tumor microenvironment. The tumor microenvironment plays important roles on gastric cancer development, progression and therapy response. In this study, we leveraged high-throughput single-cell RNA sequencing (scRNAseq) to characterize the diverse cell population in gastric tumors. In total, we analyzed more than 30,000 single cells from eight gastric tumors and matched normal tissues. Cells were sequenced at an average depth of 70000 reads/cell to guarantee sufficient coverage for downstream analysis. Using graph-based cell clustering methods and known cell markers, we identified heterogenous epithelial cells (PGC+, MUC5AC+, TFF1+, EPCAM+, CDH1+), fibroblasts (ACTA2+, THY1+, COLA1+), endothelial cells (VWF+, PECAM1+), and a variety of immune cells including M1 and M2 macrophages (IL1A+, IL1B+, TNF+, MARCO+, MSR1+, CD68+), CD4 T cells (CD3D+, CD4+), CD8 T cells (CD8A+), Gamma Delta T cells (TRGC2+, TRDC+), B cells (CD79+), and plasma cells (CD19+, CD20+, IgG+). Specifically, gastric epithelial cancer cells demonstrated distinct CNVs inferred from single cell transcriptome files. We established and characterized patient derived gastric cancer organoids from single tumor cells. The organoids recapitulate CNVs found in the original gastric tumors and displayed varied degree of drug responses. We identified specific molecular features of the tumor microenvironment that modulate cell growth and immune responses. For example, we identified heterogenous myofibroblast populations with distinct chemokine secretory profiles compared to normal gastric tissue. We characterized gene signatures associated with immune checkpoints on T cells and targetable molecules in innate cells. Using cell type specific expression profiles, we were able to establish a comprehensive signaling network of tumor-tumor, tumor-stromal, stromal-stromal and stromal-tumor signaling via receptor-ligand pairing. Citation Format: Jiamin Chen, Anuja Sathe, Sue Grimes, Stephanie Greer, Billy Lau, Ann Renschler, George Poultsides, Carlos Suarez, Hanlee Ji. Comprehensive characterization of gastric cancer at single-cell resolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 151.