Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment.

Autor: Kang B; BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China., Camps J; Biomedical Data Science, Research & Early Development Oncology, Bayer AG, Berlin, Germany., Fan B; Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China., Jiang H; Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.; Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China., Ibrahim MM; Biomedical Data Science, Research & Early Development preMed, Bayer AG, Wuppertal, Germany., Hu X; BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China., Qin S; BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China., Kirchhoff D; Immuno Oncology, Research & Early Development Oncology, Bayer AG, Berlin, Germany., Chiang DY; Biomedical Data Science, Research & Early Development Oncology, Bayer US, Cambridge, MA, USA., Wang S; Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.; Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China.; Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China., Ye Y; Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.; Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China.; Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China., Shen Z; Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China. shenzhanlong@pkuph.edu.cn.; Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China. shenzhanlong@pkuph.edu.cn.; Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China. shenzhanlong@pkuph.edu.cn., Bu Z; Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China. buzhaode@cjcrcn.org., Zhang Z; BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China. zemin@pku.edu.cn.; Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. zemin@pku.edu.cn., Roider HG; Oncology Precision Medicine, Research & Early Development Oncology, Bayer AG, Berlin, Germany. helge.roider@bayer.com.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2022 Dec 22; Vol. 23 (1), pp. 265. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1186/s13059-022-02828-2
Abstrakt: Background: The tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized.
Results: We combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival.
Conclusions: Our gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy.
(© 2022. The Author(s).)
Databáze: MEDLINE
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