Cited by 999Cancer Immunotherapy and BiomarkersGastric Cancer Management and OutcomesImmune cells in cancer

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Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures

Zeng, Dongqiang, Li, Meiyi, Zhou, Rui, Zhang, Jingwen, Sun, Huiying, Shi, Min, Bin, Jianping, Liao, Yulin, Rao, Jinjun, Liao, Wangjun·2019·Cancer Immunology Research

DOI 10.1158/2326-6066.cir-18-0436

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Abstract

Tumor microenvironment (TME) cells constitute a vital element of tumor tissue. Increasing evidence has elucidated their clinicopathologic significance in predicting outcomes and therapeutic efficacy. Nonetheless, no studies have reported a systematic analysis of cellular interactions in the TME. In this study, we comprehensively estimated the TME infiltration patterns of 1,524 gastric cancer patients and systematically correlated the TME phenotypes with genomic characteristics and clinicopathologic features of gastric cancer using two proposed computational algorithms. Three TME phenotypes were defined, and the TMEscore was constructed using principal component analysis algorithms. The high TMEscore subtype was characterized by immune activation and response to virus and IFNγ. Activation of transforming growth factor β, epithelial–mesenchymal transition, and angiogenesis pathways were observed in the low TMEscore subtype, which are considered T-cell suppressive and may be responsible for significantly worse prognosis in gastric cancer [hazard ratio (HR), 0.42; 95% confidence interval (CI), 0.33–0.54; P < 0.001]. Multivariate analysis revealed that the TMEscore was an independent prognostic biomarker, and its value in predicting immunotherapeutic outcomes was also confirmed (IMvigor210 cohort: HR, 0.63; 95% CI, 0.46–0.89; P = 0.008; GSE78220 cohort: HR, 0.25; 95% CI, 0.07–0.89; P = 0.021). Depicting a comprehensive landscape of the TME characteristics of gastric cancer may, therefore, help to interpret the responses of gastric tumors to immunotherapies and provide new strategies for the treatment of cancers.

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Additional file 3 of Immune landscape of advanced gastric cancer tumor microenvironment identifies immunotherapeutic relevant gene signature
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Additional file 7 of HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells
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Additional file 6 of H3K4me3-related lncRNAs signature and comprehensive analysis of H3K4me3 regulating tumor immunity in lung adenocarcinoma
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Additional file 4 of Identification of the expression patterns and potential prognostic role of m6A-RNA methylation regulators in Wilms Tumor
Jia, C., Gao, H., Ma, W., Liu, X., Chang, M., & Sun, F. (2023) · Figshare · doi:10.6084/m9.figshare.24180794
Additional file 4 of Bioinformatics analysis of diagnostic biomarkers for Alzheimer's disease in peripheral blood based on sex differences and support vector machine algorithm
Ji, W., An, K., Wang, C., & Wang, S. (2022) · Figshare · doi:10.6084/m9.figshare.21275962
Additional file 7 of Identification of the expression patterns and potential prognostic role of m6A-RNA methylation regulators in Wilms Tumor
Jia, C., Gao, H., Ma, W., Liu, X., Chang, M., & Sun, F. (2023) · Figshare · doi:10.6084/m9.figshare.24180803
Additional file 20 of Tumor stemness score to estimate epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) characterization and to predict the prognosis and immunotherapy response in bladder urothelial carcinoma
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Additional file 7 of H3K4me3-related lncRNAs signature and comprehensive analysis of H3K4me3 regulating tumor immunity in lung adenocarcinoma
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Additional file 7 of Bioinformatics analysis of diagnostic biomarkers for Alzheimer's disease in peripheral blood based on sex differences and support vector machine algorithm
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Additional file 2 of HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells
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Additional file 8 of Identification of the expression patterns and potential prognostic role of m6A-RNA methylation regulators in Wilms Tumor
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Additional file 6 of Identification of the expression patterns and potential prognostic role of m6A-RNA methylation regulators in Wilms Tumor
Jia, C., Gao, H., Ma, W., Liu, X., Chang, M., & Sun, F. (2023) · Figshare · doi:10.6084/m9.figshare.24180800
Additional file 3 of HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells
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Additional file 5 of Bioinformatics analysis of diagnostic biomarkers for Alzheimer's disease in peripheral blood based on sex differences and support vector machine algorithm
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Additional file 5 of HNRNPC, a predictor of prognosis and immunotherapy response based on bioinformatics analysis, is related to proliferation and invasion of NSCLC cells
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Authors: Zeng, D., Li, M., Zhou, R., Zhang, J., Sun, H., Shi, M., Bin, J., Liao, Y., Rao, J., & Liao, W.
Affiliations: Nanfang Hospital (CN)
Southern Medical University (CN)
ORCID: Zeng, Dongqiang
Li, Meiyi
Zhou, Rui
Zhang, Jingwen
Sun, Huiying
Shi, Min
Bin, Jianping
Liao, Yulin
Liao, Wangjun
Venue: Cancer Immunology Research
Publisher: American Association for Cancer Research (AACR)
Published: 2019-05-01
Volume: 7
Issue: 5
Pages: 737-750
ISSN: 2326-6066 (ISSN-L)
2326-6074
DOI: 10.1158/2326-6066.cir-18-0436
OpenAlex: W2920600229
Semantic Scholar: 180648d1827a7e8c086f03b00ca69831a1ca538e
Cited by: 986
References: 76
Citations by year: 2026: 38 · 2025: 87 · 2024: 164 · 2023: 211 · 2022: 251 · 2021: 162 · 2020: 64 · 2019: 9
FWCI: 53.10
Type: journal article
Language: en
Open access: closed
Locations: Cancer Immunology Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81772580)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Oncology › Gastric Cancer Management and Outcomes
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: gastric cancer, tumor microenvironment, prognostic factors, immunotherapy response, immune cell infiltration, T cell suppression, epithelial-mesenchymal transition, angiogenesis, TGF-beta signaling, IFN-gamma response, gene expression signatures, IMvigor210
MeSH terms: Antineoplastic Agents, Immunological, Algorithms, Humans, Immunotherapy, Phenotype, Prognosis, Stomach Neoplasms, Gene Expression Regulation, Neoplastic, Tumor Microenvironment

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Tumor Microenvironment Characterization in Gastric Cancer Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures

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