Spatially Resolved Tumor Ecosystems and Cell States in Gastric Adenocarcinoma Progression and Evolution

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Authors: Haoran Ma ; Supriya Srivastava ; Shamaine Wei Ting Ho ; Chang Xu ; Benedict Shi Xiang Lian ; Xuewen Ong ; Su Ting Tay ; Taotao Sheng ; Huey Yew Jeffrey Lum ; Siti Aishah Binte Abdul Ghani ; Yunqiang Chu ; Kie Kyon Huang ; Yeek Teck Goh ; Minghui Lee ; Takeshi Hagihara ; Clara Shi Ya Ng ; Angie Lay Keng Tan ; Yanrong Zhang ; Zichen Ding ; Feng Zhu ; Michelle Shu Wen Ng ; Craig Ryan Cecil Joseph ; Hui Chen ; Zhen Li ; Joseph J Zhao ; Sun Young Rha ; Ming Teh ; Joe Yeong ; Wei Peng Yong ; Jimmy Bok-Yan So ; Raghav Sundar ; Patrick Tan

MeSH: Adenocarcinoma* / genetics ; Adenocarcinoma* / pathology ; Disease Progression ; Humans ; Single-Cell Analysis ; Stomach Neoplasms* / genetics ; Stomach Neoplasms* / pathology ; Tumor Microenvironment* / genetics

Abstract: Integration of spatial transcriptomic (GeoMx Digital Spatial Profiler) and single-cell RNA sequencing data from multiple gastric cancers identifies spatially resolved expression-based intratumoral heterogeneity, associated with distinct immune microenvironments. We uncovered two separate evolutionary trajectories associated with specific molecular subtypes, clinical prognoses, stromal neighborhoods, and genetic drivers. Tumor-stroma interfaces emerged as a unique state of tumor ecology.