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

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 a...

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Vydané v:Genome Biology Ročník 23; číslo 1; s. 265
Hlavní autori: Kang, Boxi, Camps, Jordi, Fan, Biao, Jiang, Hongpeng, Ibrahim, Mahmoud M., Hu, Xueda, Qin, Shishang, Kirchhoff, Dennis, Chiang, Derek Y., Wang, Shan, Ye, Yingjiang, Shen, Zhanlong, Bu, Zhaode, Zhang, Zemin, Roider, Helge G.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 22.12.2022
BMC
Predmet:
Animal Genetics and Genomics
Bioinformatics
biomarkers
Biomedical and Life Sciences
Endothelial Cells
Evolutionary Biology
fibroblasts
Gastric cancer
Gene Expression Profiling
genome
Human Genetics
Humans
immunosuppression
Life Sciences
macrophages
Microbial Genetics and Genomics
patients
Plant Genetics and Genomics
prognosis
RNA
Single-Cell Analysis
Single-cell RNA transcriptomics
stomach
stomach neoplasms
Stomach Neoplasms - genetics
therapeutics
transcription (genetics)
Transcriptome
Tumor Microenvironment
Single-cell RNA transcriptomics
Tumor microenvironment
Gastric cancer
ISSN:1474-760X, 1474-7596, 1474-760X
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
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content type line 23
ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-022-02828-2