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

The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.

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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MethodInfluential
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Additional file 4 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
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Additional file 8 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
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Additional file 2 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
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Additional file 12 of Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma
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Additional file 13 of H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
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Additional file 11 of H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
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Additional file 10 of H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
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Additional file 7 of Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma
Liu, Z.-T., Shen, J.-T., Lei, Y.-J., Huang, Y.-C., Zhao, G.-Q., Zheng, C.-H., Wang, X., Wang, Y.-T., Chen, L., Li, Z.-X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26644801
Additional file 1 of Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
Wang, H., Liu, Y., 唐爱发, & Zhang, X. (2024) · Figshare · doi:10.6084/m9.figshare.26723118
Additional file 4 of Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment
Zhou, H., Zheng, M., Shi, M., Wang, J., Huang, Z., Zhang, H., Zhou, Y., & Shi, J. (2021) · Figshare · doi:10.6084/m9.figshare.15982375
Self-citation
Additional file 4 of N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma
Xu, H., Yin, L., Xu, Q., Xiang, J., & Xu, R. (2022) · Figshare · doi:10.6084/m9.figshare.19862420
Additional file 10 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
Liu, X., Zheng, Y., Xiao, M., Chen, X., Zhu, Y., Xu, C., Wang, F., Liu, Z., & Cao, K. (2024) · Figshare · doi:10.6084/m9.figshare.26556179
Additional file 15 of Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma
Liu, Z.-T., Shen, J.-T., Lei, Y.-J., Huang, Y.-C., Zhao, G.-Q., Zheng, C.-H., Wang, X., Wang, Y.-T., Chen, L., Li, Z.-X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26644825
Additional file 1 of Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma
Tan, S., Guo, X., Bei, C., Zhang, H., Li, D., Zhu, X., & Tan, H. (2022) · Figshare · doi:10.6084/m9.figshare.20521508
Additional file 11 of Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma
Liu, Z.-T., Shen, J.-T., Lei, Y.-J., Huang, Y.-C., Zhao, G.-Q., Zheng, C.-H., Wang, X., Wang, Y.-T., Chen, L., Li, Z.-X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26644813
Additional file 4 of Identification and validation of pyroptosis-related gene landscape in prognosis and immunotherapy of ovarian cancer
Gao, L., Ying, F., Cai, J., Peng, M., Xiao, M., Sun, S., Zeng, Y., 熊宙芳, Cai, L., Gao, R., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22604774
Additional file 6 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
Liu, X., Zheng, Y., Xiao, M., Chen, X., Zhu, Y., Xu, C., Wang, F., Liu, Z., & Cao, K. (2024) · Figshare · doi:10.6084/m9.figshare.26556167
Additional file 9 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
Zhang, Y., Zhang, X., Huang, X., Tang, X., Zhang, M., Li, Z., Hu, X., Zhang, M., Wang, X., & Yan, Y. (2023) · Figshare · doi:10.6084/m9.figshare.22609514
Additional file 1 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
Zhang, Y., Zhang, X., Huang, X., Tang, X., Zhang, M., Li, Z., Hu, X., Zhang, M., Wang, X., & Yan, Y. (2023) · Figshare · doi:10.6084/m9.figshare.22609487
Additional file 8 of Identification and validation of pyroptosis-related gene landscape in prognosis and immunotherapy of ovarian cancer
Gao, L., Ying, F., Cai, J., Peng, M., Xiao, M., Sun, S., Zeng, Y., 熊宙芳, Cai, L., Gao, R., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22604786
Additional file 1 of A signature of six-hypoxia-related genes to evaluate the tumor immune microenvironment and predict prognosis in gastric cancer
Zhou, K., Cai, C., Ding, G., He, Y., & Hu, D. (2024) · Figshare · doi:10.6084/m9.figshare.26555045
Additional file 2 of N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma
Xu, H., Yin, L., Xu, Q., Xiang, J., & Xu, R. (2022) · Figshare · doi:10.6084/m9.figshare.19862414
Additional file 3 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
Zhang, Y., Zhang, X., Huang, X., Tang, X., Zhang, M., Li, Z., Hu, X., Zhang, M., Wang, X., & Yan, Y. (2023) · Figshare · doi:10.6084/m9.figshare.22609493
Additional file 8 of Cross talk between acetylation and methylation regulators reveals histone modifier expression patterns posing prognostic and therapeutic implications on patients with colon cancer
Zhou, R., Xie, F., Liu, K., Zhou, X., Chen, X., Chen, J., Xi, S., Huang, Z., & Rong, X. (2022) · Figshare · doi:10.6084/m9.figshare.19845928
Self-citation
Additional file 5 of Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response
Wu, J., Zeng, D., Zhi, S., Ye, Z., Qiu, W., Huang, N., Sun, L., Wang, C., Wu, Z., Bin, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16590905
Self-citation
Additional file 2 of Machine learning and bioinformatics analysis revealed classification and potential treatment strategy in stage 3–4 NSCLC patients
Li, C., Tian, C., Zeng, Y., Liang, J., Yang, Q., Gu, F., Hu, Y., & Liu, L. (2022) · Figshare · doi:10.6084/m9.figshare.19218822
Additional file 5 of Glucose transporter 3 (GLUT3) promotes lactylation modifications by regulating lactate dehydrogenase A (LDHA) in gastric cancer
Yang, H., Yang, S., He, J., Li, W., Zhang, A., Li, N., Zhou, G., & Sun, B. (2024) · Figshare · doi:10.6084/m9.figshare.26648262
Additional file 2 of Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment
Zhou, H., Zheng, M., Shi, M., Wang, J., Huang, Z., Zhang, H., Zhou, Y., & Shi, J. (2021) · Figshare · doi:10.6084/m9.figshare.15982369
Self-citation
Additional file 1 of Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer
Liu, S.-S., Wan, Q., Lv, C., Wang, J.-K., Jiang, S., Cai, D., Liu, M.-S., Wang, T., & Zhang, K.-H. (2024) · Figshare · doi:10.6084/m9.figshare.25608680
Additional file 1 of Machine learning and bioinformatics analysis revealed classification and potential treatment strategy in stage 3–4 NSCLC patients
Li, C., Tian, C., Zeng, Y., Liang, J., Yang, Q., Gu, F., Hu, Y., & Liu, L. (2022) · Figshare · doi:10.6084/m9.figshare.19218816
Additional file 5 of Identification of novel antioxidant gene signature to predict the prognosis of patients with gastric cancer
Wu, J., Wang, X., Wang, N., Ma, L., Xie, X., Zhang, H., Kang, H., & Zhou, Z. (2021) · Figshare · doi:10.6084/m9.figshare.15026673
Additional file 6 of Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma
Liu, Z.-T., Shen, J.-T., Lei, Y.-J., Huang, Y.-C., Zhao, G.-Q., Zheng, C.-H., Wang, X., Wang, Y.-T., Chen, L., Li, Z.-X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26644798
Additional file 5 of N6-methyladenosine methylation modification patterns reveal immune profiling in pancreatic adenocarcinoma
Xu, H., Yin, L., Xu, Q., Xiang, J., & Xu, R. (2022) · Figshare · doi:10.6084/m9.figshare.19862423
Additional file 1 of The expression pattern of immune-related genes and characterization of tumor immune microenvironment: predicting prognosis and immunotherapeutic effects in cutaneous melanoma
Dong, D., Wang, W., Wang, H., Chen, L., & Liu, T. (2022) · Figshare · doi:10.6084/m9.figshare.21191986
Additional file 2 of A signature of six-hypoxia-related genes to evaluate the tumor immune microenvironment and predict prognosis in gastric cancer
Zhou, K., Cai, C., Ding, G., He, Y., & Hu, D. (2024) · Figshare · doi:10.6084/m9.figshare.26555048
Additional file 1 of A signature of 24 aging‑related gene pairs predict overall survival in gastric cancer
Zhang, Y., Yan, Y., Ning, N., Shen, Z., & Ye, Y. (2021) · Figshare · doi:10.6084/m9.figshare.14379582
Additional file 2 of Development of a machine learning-based radiomics signature for estimating breast cancer TME phenotypes and predicting anti-PD-1/PD-L1 immunotherapy response
Han, X., Guo, Y., Ye, H., Chen, Z., Hu, Q., Wei, X., Liu, Z., & Liang, C. (2024) · Figshare · doi:10.6084/m9.figshare.25107911
Additional file 3 of Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies
Wang, H., Liu, Y., 唐爱发, & Zhang, X. (2024) · Figshare · doi:10.6084/m9.figshare.26723124
Additional file 9 of H4-methylation regulators mediated epitranscriptome patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma
Yu, L., Ji, T., Liao, W., Xu, Y., Fang, Y., Zhu, Q., Nie, J., & Yang, D. (2023) · Figshare · doi:10.6084/m9.figshare.22624213
Self-citation
Additional file 1 of A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment
Gong, X., Zheng, C., Jia, H., Liu, Y., Yang, R., Chen, Z., Pan, Y., Li, X., & Liu, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26636397
Additional file 5 of SRSF10 stabilizes CDC25A by triggering exon 6 skipping to promote hepatocarcinogenesis
Liu, X., Zheng, Y., Xiao, M., Chen, X., Zhu, Y., Xu, C., Wang, F., Liu, Z., & Cao, K. (2024) · Figshare · doi:10.6084/m9.figshare.26556164

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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