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

IF 29.7 1区医学 Q1 ONCOLOGY

Cancer discovery Pub Date : 2025-01-08 DOI:10.1158/2159-8290.cd-24-0605

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

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引用次数: 0

Abstract

Gastric cancer (GC) is a major cause of global cancer mortality with high levels of heterogeneity. To explore geospatial interactions in tumor ecosystems, we integrated 2,138 spatial transcriptomic regions-of-interest (ROIs) with 152,423 single-cell expression profiles across 226 GC samples from 121 patients. We observed pervasive expression-based intratumor heterogeneity, recapitulating tumor progression through spatially localized and functionally ordered subgroups associated with specific immune microenvironments, checkpoint profiles, and genetic drivers such as SOX9. Evolutionary phylogenetic analysis revealed two different evolutionary trajectories (branched evolution and internal diaspora evolution) associated with distinct molecular subtypes, clinical prognoses, and stromal neighborhoods including VWF+ ACKR1+ endothelial cells. Spatial analysis of tumor-stromal interfaces across multiple GCs highlighted new ecosystem states not attributable to mere tumor/stroma admixture, landmarked by increased GREM1 expression. Our results provide insights into how the cellular ecosystems of individual GCs are sculpted by tumor intrinsic and extrinsic selective pressures, culminating in individualized patient-specific cancer cartographies.

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来源期刊

Cancer discovery ONCOLOGY-

CiteScore

22.90

自引率

1.40%

发文量

838

审稿时长

6-12 weeks

期刊介绍： Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.