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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Items 401–500 of 999

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Background
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“Of course, both TME and immune scoring are different in different subtypes, which may also lead to different prognostic and immunotherapeutic outcomes (25, 26).”
Background
The Pan-Cancer Landscape of Crosstalk Between TRP Family and Tumour Microenvironment Relevant to Prognosis and Immunotherapy Response
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Method
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Method
TMEM92 acts as an immune-resistance and prognostic marker in pancreatic cancer from the perspective of predictive, preventive, and personalized medicine
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Method
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MethodSelf-citation
Comprehensive Pan-Cancer Analysis of Senescence With Cancer Prognosis and Immunotherapy
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“, 2016; He and Sharpless, 2017), we also paid more attention to immune-related and other biological processes (Zeng et al., 2019).”
Background
Predictive value of drug efficacy by M6A modification patterns in rheumatoid arthritis patients
Song, S., Zhao, R., Qiao, J., Liu, J., Cheng, T., Zhang, S., & Li, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940918 · Cited by 9
“We then define the m6Ascore by adopting a formula like previous studies (18, 20, 21).”
Method
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“The pan-fibroblast TGF-beta response signature (F-TBRS) and the TMEscore are both calculated using the principal component analysis (PCA) of the signature genes [32,33].”
Method
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“In contrast, in fact, it was identified as part of an immunogenic signature during the transcriptomic characterization of the GC tumor microenvironment [46].”
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“The tumor microenvironment (TME), which contains diverse immune cell populations, is thought to play a crucial role in the development of different cancers, including breast cancer (6), gastric cancer, (7) and esophageal squamous cell carcinoma (ESCC) (8), which suggest that immune cell infiltration may be associated…”
Background
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Luo, H., Ye, M., Hu, Y. W., Wu, M., Cheng, M., Zhu, X., & Huang, K. (2022) · Aging · doi:10.18632/aging.204291 · Cited by 9
“DEGs and was calculated as follows: DMS = ∑ (PC1i + PC2i), where i, represents the expression of survivalassociated DEGs expression in the cohort of glioma patients [52, 53].”
Method
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Yuan, S., Gao, Y., Xia, Y., Wang, Z., & Wang, X. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.1008644 · Cited by 9
“At last, we investigated several molecules, including chemokines and cytokines associated with immune activation or suppression, which were referenced from published literature (Zeng et al., 2019).”
Background
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Hu, B., Meng, Y., Qu, C., Wang, B., & Xiu, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018413 · Cited by 9
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Wang, Y., Gao, P., Hao, Z., Ling, C., Li, X., Yuan, J., Liu, J., Li, J., Zhang, Y., Peng, X., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1054598 · Cited by 10
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“High infiltration level of macrophages is correlated with a poor overall survival rate of GC, which has a correlation in promoting inflammation, angiogenesis, hypoxia pathway, and avoiding immune surveillance (Zeng et al., 2019; Gambardella et al., 2020).”
Background
Construction and validation of a signature for T cell-positive regulators related to tumor microenvironment and heterogeneity of gastric cancer
Guo, Y., Zhang, Y., Cen, K., Dai, Y., Mai, Y., & Hong, K. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1125203 · Cited by 8
“TME was revealed to be substantially relevant to gastric cancer, both at the genomic and clinical levels (28).”
Background
Defining Tumor Microenvironment as a Possible Target for Effective GEP-NENs Immunotherapy—A Systematic Review
Chmiel, P., Rychcik-Pazyrska, P., & Stec, R. (2023) · Cancers · doi:10.3390/cancers15215232 · Cited by 10
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Lyu, X., Wang, P., Qiao, Q., & Jiang, Y. (2021) · BMC Cancer · doi:10.1186/s12885-021-08350-1 · Cited by 9
“The role of tumour-infiltrating lymphocytes (TILs) and cytokines in immunotherapy has been demonstrated [13].”
Background
A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer
Liu, F., Yang, Z., Zheng, L., Shao, W., Cui, X., Wang, Y., Jia, J., & Fu, Y. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.690129 · Cited by 9
An Immune-Related Prognostic Classifier Is Associated with Diffuse Large B Cell Lymphoma Microenvironment
Liang, X., Fu, R., Wang, H.-N., Yang, J., Yao, N., Liu, X., & Wang, L. (2021) · Journal of Immunology Research · doi:10.1155/2021/5564568 · Cited by 9
Tumor Immune Microenvironment Landscape in Glioma Identifies a Prognostic and Immunotherapeutic Signature
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Evaluation of Immune Infiltration Based on Image Plus Helps Predict the Prognosis of Stage III Gastric Cancer Patients with Significantly Different Outcomes in Northeastern China
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“It is generally believed that certain immune cells in tumor tissues can secrete a large number of inflammatory factors, reactive oxygen species to destroy the matrix in the tumor microenvironment [32], kill normal cells, and promote tumor invasion [33–35].”
Background
Tumor Microenvironment-Mediated Immune Profiles Characterized by Distinct Survival Outcome and Immunotherapeutic Efficacy in Breast Cancer
Xu, L., Hu, Y., & Liu, W. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.840348 · Cited by 9
“However, approximately one-third of patients fail to respond to these therapeutic agents, and numerous studies have demonstrated that microsatellite instability, PD-L1/PD-1 expression, and TMB are not efficient predictors of the efficacy of immunotherapies (Zeng et al., 2019; Tang et al., 2020).”
Background
Pyroptosis-Related Signature and Tumor Microenvironment Infiltration Characterization in Head and Neck Squamous Cell Carcinoma
Wu, Z., Wu, B., Li, C., Zhang, Y., & Zhou, T. Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.702224 · Cited by 9
“Thus, the PyroptosisScore was acquired based on the formula (Zeng et al., 2019): PyroptosisScore = ∑(PC1i + PC2i).”
Method
Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor
Tang, E., Zhou, Y., Liu, S. M., Zhang, Z., Zhang, R., Huang, D., Gao, T., Zhang, T., & Xu, G. (2022) · Metabolites · doi:10.3390/metabo12060567 · Cited by 9
“Finally, a formula similar to that in previous studies [42,43] was applied to define the metabolic score:”
Method
Identification of Survival Risk and Immune-Related Characteristics of Kidney Renal Clear Cell Carcinoma
Wu, X., Liang, Y., Chen, X., Long, X., Xu, W., Liu, L., Wang, B., & Zou, X. (2022) · Journal of Immunology Research · doi:10.1155/2022/6149369 · Cited by 9
“More and more studies have emphasized that there is heterogeneity in the proportion of immune-related genes and immune cell populations in tumors [11, 12], which may be one of the key reasons for di ﬀ erent prognosis of patients.”
N7-methylguanosine-related lncRNAs: Predicting the prognosis and diagnosis of colorectal cancer in the cold and hot tumors
Wu, J., Song, Q., Huang, C., Shao, Y., Wang, Z.-L., Zhang, H., & Fu, Z. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.952836 · Cited by 9
“Different immunotherapeutic responses may result from it (Zeng et al., 2019; DeBerardinis, 2020).”
Background
RNA m5C regulator-mediated modification patterns and the cross-talk between tumor microenvironment infiltration in gastric cancer
Zhang, Q., Sun, X., Sun, J., Lu, J., Gao, X., Shen, K., & Qin, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.905057 · Cited by 9
“ACTA2,CLDN3, COL4A1, SMAD9, TGRB1, TGFBR2, TWIST1, VIM, and ZEB1 are considered to associate with TGF-b and EMTpathways (24, 38).”
Background
Pan-cancer analysis of ASB3 and the potential clinical implications for immune microenvironment of glioblastoma multiforme
Mu, L., Han, Z., Yu, S., Wang, A., Chen, D., Kong, S., Gu, Y., Lin, X., Liu, A., Sun, R., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.842524 · Cited by 9
“Tumor-infiltrating immune cells play important roles in the TME, which not only provide a suitable microenvironment for the survival of tumor cells, but also are connected to the regulation of tumor immune surveillance and the response of tumor treatment (33, 34).”
Background
Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function
Wang, S., Wang, Y., Shen, A., Yang, X.-Q., Liang, C., Huang, R.-J., Jian, R., An, N., Xiao, Y.-L., Wang, L., et al. (2024) · European journal of medical research · doi:10.1186/s40001-024-01783-x · Cited by 9
“…load (NAL), copy alternation number (CAN), mismatch repair deficiency (dMMR), microsatellite instability (MSI), tumor microenvironment (TME), especially the expression of PD-1/PD-L1 and mutation of some specific genes are considered to be predictive markers of immunotherapy in GC patients [16–18].”
Background
Tumor Microenvironment Characterization in Glioblastoma Identifies Prognostic and Immunotherapeutically Relevant Gene Signatures
Zhang, J., Xiao, X., Zhang, X., & Hua, W. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01484-0 · Cited by 9
Self-citation
A new clinical prognostic nomogram for liver cancer based on immune score
Shen, Q., Hu, G., Wu, J.-Z., & Lv, L. (2020) · PLoS ONE · doi:10.1371/journal.pone.0236622 · Cited by 9
Comprehensive Study of Tumor Immune Microenvironment and Relevant Genes in Hepatocellular Carcinoma Identifies Potential Prognostic Significance
Chen, W., Zhang, X., Bi, K., Zhou, H., Xu, J. X., Dai, Y., & Diao, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.554165 · Cited by 9
“In line with prior studies, upregulation of genes associated with immune activation and immune checkpoint proteins correlates with better prognosis, whereas upregulation of genes associated with TGF/EMT correlates with poorer prognosis (14, 49).”
BackgroundResult
Classification of gastric cancers based on immunogenomic profiling
Liu, Z., Jiang, Z., Wu, N., Zhou, G., & Wang, X. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100888 · Cited by 9
Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma
Su, C., Huang, R., Yu, Z., Zheng, J., Liu, F., Liang, H., & Mo, Z. (2022) · Cancer Medicine · doi:10.1002/cam4.4542 · Cited by 9
Characterization of tumor-associated reactive astrocytes in gliomas by single-cell and bulk tumor sequencing
Zhang, C., Wang, Z.-L., Liu, H.-J., Wang, Z., & Jia, W. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1193844 · Cited by 8
“We then analyzed the differential expression of checkpoint relevant genes and cytokine and chemokine transcripts (22) between HRA and LRA groups (Figures 5C,D).”
Method
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., Liu, Y., & Liu, Y. (2023) · BMC Cancer · doi:10.1186/s12885-023-11545-3 · Cited by 8
“We also examined the associations of LFNG, MFNG, and RFNG levels with tumor-infiltrating immunocyte gene markers [25– 27].”
Background
m6A regulator-mediated methylation modification patterns and tumor microenvironment immune infiltration with prognostic analysis in esophageal cancer
Sheng, G., Wang, T., Gao, Y., Wu, H., & Wu, J. (2023) · Scientific Reports · doi:10.1038/s41598-023-46729-1 · Cited by 8
The prognostic and immune significance of PLBD1 in pan-cancer and its roles in proliferation and invasion of glioma
Wei, M., Zhou, G., Chen, L., Zhang, Y., Ma, W., Gao, L., & Gao, G. (2024) · Journal of Cancer · doi:10.7150/jca.96365 · Cited by 8
“…in the tumor microenvironment play an important role in the malignant progression of tumors, not only by providing a suitable immunosuppressive microenvironment for the survival of tumor cells, but also by being associated with tumor immunosurveillance and response to immunotherapy [35].”
Background
Deep learning model targeting cancer surrounding tissues for accurate cancer diagnosis based on histopathological images
Li, L., Geng, Y., Chen, T., Lin, K., Xie, C., Qi, J., Wei, H., Wang, J., Wang, D., Yuan, Z., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-06017-6 · Cited by 8
“They result in different morphologic characteristics, texture and spatial arrangement of TME, form a unique landscape around the cancer cells and may become the mechanism of tumor progression or the prediction of patients’ prognosis [51, 52].”
Prognostic implications and characterization of tumor-associated tertiary lymphoid structures genes in pancreatic cancer
Zhang, E., Ma, Y., Liu, Z., Zhang, J., Liu, W., Chen, Y., Liu, G., Liu, X., Zhang, F., Zhu, Y., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06152-8 · Cited by 8
“Subsequently, we conducted a differential analysis of biological processes based on previously summarized TME characteristics [31] for the TLS molecular patterns (Fig.”
Self-citation
Comprehensive immunophenotyping of gastric adenocarcinoma identifies an inflamed class of tumors amenable to immunotherapies
Rodríguez, J. V., Piñol, M., Sorolla, M. A., Parisi, E., Sorolla, A., Santacana, M., Ruiz, M., Parra, G., Aracil, M. B. B., Iglesias, M., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010024 · Cited by 10
“…other studies have published tumor microenvironment scores based on the association of gene expression with prognosis 41 or response to ICIs 42 in cohorts of GAC, although the usefulness of these signatures is dependent on the specific purpose of their design, not being a holistic descriptive…”
Correlation of CLDN18.2 and Tumor Microenvironment in Gastric Cancer: A Systematic Review
Zarampouka, K., Tsiantas, C., Stavropoulou, M. A., Efthymiadis, K., Theotokis, P., Gargani, S., Vrettou, E., Κoletsa, T., Μanthou, M. E., & Meditskou, S. (2025) · Cancers · doi:10.3390/cancers17132120 · Cited by 8
“The tumor microenvironment is made up of the extracellular matrix and includes a variety of cells like cancer cells, cancer-associated fibroblasts (CAFs), pericytes, and immune cells [47,48].”
Multi-omics analysis uncovers predictive biomarkers for the efficacy and outcomes of chemoimmunotherapy in advanced unresectable biliary tract cancers
Ni, J., Li, C., Xu, X., Xu, Q., Yin, Q., Chen, H., Zhou, S., Li, J., Zheng, Q., Xie, Y., et al. (2025) · BMC Medicine · doi:10.1186/s12916-025-04263-z · Cited by 9
“Tumor microenvironment (TME) scores were estimated using the R package TMEscore (https:// github. com/ Dongq iangZ eng08 08/ TMEsc ore) [30].”
Integrative single-cell, spatial, and bulk transcriptomics reveal an FMR1–FTO axis linked to the immune-excluded phenotype in gastric cancer
Mao, C., Zhang, M., Zhou, K., Hong, Y., Han, Y., Zhao, L., Liang, M., Zhang, J., Hu, N., & 吴风雷 (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1713267 · Cited by 8
Self-citation
An Autophagy-Related Gene Signature can Better Predict Prognosis and Resistance in Diffuse Large B-Cell Lymphoma
Zhou, X., He, Y., Liu, D., Lin, C.-R., Liang, D., Huang, R., & Wang, L. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.862179 · Cited by 8
m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia
Xu, Z., Wen, X.-M., Zhang, Y.-C., Jin, Y., Ma, J., Gu, Y., Chen, X., Xia, P., Qian, W., Lin, J., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.948079 · Cited by 8
“As a result, the m6Ascore was calculated as follows: m6Ascore = Σ(PC1i + PC2i), where i was the expression of m6A phenotype-related genes (Zeng et al., 2019).”
Method
Prediction of prognosis, immune infiltration and immunotherapy response with N6-methyladenosine-related lncRNA clustering patterns in cervical cancer
Jia, H., Cao, M., Hao, S., Wang, J., & Wang, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-20162-2 · Cited by 8
Dendritic cell maturation in the tumor microenvironment
Miao, Y., Liu, Y., Tang, H., & Zhang, Z. (2023) · National Science Open · doi:10.1360/nso/20220053 · Cited by 9
“Likewise, in gastric cancer, the TME features with high expression of mature DC signature genes are also better for prognosis than the TME features containing immature DCs [44].”
Background
The prognostic and immunological role of FKBP1A in an integrated muti-omics cancers analysis, especially lung cancer
Zhang, Y., Xu, H., Pi, S., Tan, H., Huang, B., & Chen, Y. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-05362-1 · Cited by 8
“TME feature is regarded as a potential marker to predict the response of immunotherapy (Zeng et al. 2019).”
Background
Prognostic value of PD‑L1 expression and CD68 macrophages in tumor nest of patients with primary gastric cancer
Zou, Y., Wang, J., Zhang, J., Guo, Q., Song, Z., & Tang, H. (2023) · Oncology Letters · doi:10.3892/ol.2023.14153 · Cited by 8
“Moreover, over the last several years, an increasing number of studies have found that PD‑L1 expressed on immune cells in the TME is closely related to patient prognosis (13,25).”
Self-citation
BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer
Zhang, W., Yu, L., Chang, Z., & Xiong, H. (2023) · Journal of Cancer · doi:10.7150/jca.90085 · Cited by 8
“Correlation analysis between the tumor microenvironment and FLT3LG was performed using the method described in a previous article( 13 ).”
Method
Integrative analysis of the cuproptosis-related gene ATP7B in the prognosis and immune infiltration of IDH1 wild-type glioma
Zhang, K., Qu, C., Zhou, P., Yang, Z., & Wu, X. (2024) · Gene · doi:10.1016/j.gene.2024.148220 · Cited by 8
Identification and validation of immunity- and disulfidptosis-related genes signature for predicting prognosis in ovarian cancer
Jin, M., Ni, D., Cai, J., & Yang, J. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e32273 · Cited by 8
“Subsequently, the DRGscore was determined with a methodology that closely resembles the GGI: Where i is the expression of disulfidptosis-related genes [19,20].”
Method
Single-cell RNA Sequencing Analysis Reveals Cancer-associated Fibroblast Signature for Prediction of Clinical Outcomes and Immunotherapy in Gastric Cancer
Li, X., Tang, B., Yujie, O., Xu, C. S., & Yuan, S. (2024) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000539 · Cited by 8
Fundamentals of Digestive Cancers Immunology, Especially Gastric and Hepatocellular CarcinomasFondamentaux de l’immunologie des Cancers Digestifs (Gastriques et Hépatocellulaires)
Poureau, P.-G., & Metges, J. (2021) · ONCOLOGIE · doi:10.32604/oncologie.2021.15525 · Cited by 8
A Novel RNA-Binding Protein Signature to Predict Clinical Outcomes and Guide Clinical Therapy in Gastric Cancer
Qiu, Z., Jiang, H., Ju, K., & Liu, X. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.670141 · Cited by 8
“Increasing evidence has highlighted clinicopathologic implication of immune microenvironment in survival outcomes and therapeutic efficacy in gastric cancer (12).”
Background
Comprehensive Analysis of N6-methyladenosine Modification Patterns Associated With Multiomic Characteristics of Bladder Cancer
Liu, J., Wang, J., Wu, M. Y., Zhang, W., Meng, L., Wang, J., Lv, Z., Xia, H., Zhang, Y., & Wang, J. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.757432 · Cited by 8
“This method can increase the weight coefficient of genes significantly related to other genes and reduce the influence of genes not related to other genes (20).”
Method
Multi-Omics Analyses Revealed GOLT1B as a Potential Prognostic Gene in Breast Cancer Probably Regulating the Immune Microenvironment
Liu, J., Zhang, W., Cai, W., Chen, Y., Cai, X., Tang, D., Tang, M., & Dai, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.805273 · Cited by 8
“Bioinformatics The immune infiltration were investigated using CIBERSORT database following a standard protocol (9).”
Method
[Retracted] Characterization of Tumor Mutation Burden‐Based Gene Signature and Molecular Subtypes to Assist Precision Treatment in Gastric Cancer
Cheng, W., Li, M., Lin, S., & Xiao, J. (2022) · BioMed Research International · doi:10.1155/2022/4006507 · Cited by 8
“Much research has demonstrated that tumor cells display altered biological behaviors by interactions with tumor immune microenvironment components [35, 36].”
BackgroundSelf-citation
Retracted
Dysregulated Immune and Metabolic Microenvironment Is Associated with the Post-Operative Relapse in Stage I Non-Small Cell Lung Cancer
Zhang, S., Xiao, X., Zhu, X., Chen, X., Zhang, X., Xiang, J., Xu, R., Shao, Z., Bai, J., Xun, Y., et al. (2022) · Cancers · doi:10.3390/cancers14133061 · Cited by 9
Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma
Wu, K., Liu, Z., Liang, J., Zhang, F., Zhang, F., Wang, Y., Lia, T., Liu, S., Zhu, Y., & Li, X. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.903824 · Cited by 8
“Further, SIGLEC15, TIGIT, CD274, HAVCR2, PDCD1, CTLA4, LAG3 and PDCD1LG2 were selected to be immune-checkpoint– relevant transcripts (24), and the expression values of these eight genes were compared in the GR-high and GR-low groups.”
Background
Molecular characterization, clinical relevance and immune feature of m7G regulator genes across 33 cancer types
Li, Z., Li, Y., Shen, L., Shen, L., & Li, N. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.981567 · Cited by 8
“Therefore, we evaluated several biological processes connected to TME (Zeng et al., 2019), including immune related pathways (antigen processing machinery, immune checkpoint, CD8 T-effector), matrix/ metastasis related pathways (EMT1, EMT2, EMT3, pan fibroblast TGF-β response signature), and DNA damage/repair related…”
MethodInfluential
Identification of two robust subclasses of sepsis with both prognostic and therapeutic values based on machine learning analysis
Zhou, W. M., Zhang, C., Zhuang, Z., Zhang, J., & Zhong, C. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1040286 · Cited by 9
Self-citation
Development of a risk model to predict prognosis in breast cancer based on cGAS-STING-related genes
Chen, C., Wang, J., Dong, C., LIM, D. J., & Feng, Z. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1121018 · Cited by 8
“studies revealed that TME status were valuable predictive indicators for tumor immune response (Zeng et al., 2019; Chen et al., 2021; Wu et al., 2021).”
Background
Bioinformatics-guided analysis uncovers TIGIT as an epigenetically regulated immunomodulator affecting immunotherapeutic sensitivity of gastric cancer
Ma, J. (2021) · Cancer Biomarkers · doi:10.3233/cbm-210159 · Cited by 7
“Tumor immune microenvironment and individual immune landscape are found to be signiﬁcant determinant affecting the prognosis and immunotherapeutic response of gastric cancer [22].”
Inflammation-related indicators to distinguish between gastric stromal tumors and leiomyomas: A retrospective study
Zhai, Y., Zheng, Z., Deng, W., Yin, J., Bai, Z., Liu, X., Zhang, J., & Zhang, Z.-T. (2022) · World Journal of Clinical Cases · doi:10.12998/wjcc.v10.i2.458 · Cited by 8
Self-citation
IOBR2: Multidimensional Decoding Tumor Microenvironment for Immuno-Oncology ResearchPreprint
Zeng, D., Fang, Y., Luo, P., Qiu, W., Wang, S., Shen, R., Gu, W., Huang, X., Mao, Q., Lai, Y.-H., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.13.575484 · Cited by 8
Self-citation
How does TCR-T cell therapy exhibit a superior anti-tumor efficacy
Yang, D., Duan, Z., Yuan, P., Ding, C., Dai, X., Chen, G., & Wu, D. (2023) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2023.149209 · Cited by 7
Multi-omic analysis and validation reveal ZBP1 as a potential prognostic and immunotherapy-related biomarker in head and neck squamous cell carcinoma
Li, Y., Wang, N., & Yang, G. (2024) · Journal of Stomatology Oral and Maxillofacial Surgery · doi:10.1016/j.jormas.2024.101901 · Cited by 7
The complement C3a/C3aR pathway is associated with treatment resistance to gemcitabine-based neoadjuvant therapy in pancreatic cancer
Shi, S., Ye, L., Jin, K., Yu, X., Guo, D., & Wu, W. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.09.032 · Cited by 7
β-Blockers Influence Oncological Outcomes in Gastric Cancer Patients Treated with Neoadjuvant Chemotherapy Based on the Pathological Subtype: A Retrospective Cohort Study
Crnovrsanin, N., Zumsande, S., Rompen, I. F., Schiefer, S., Zimmer, S., Hu, W., Arnscheidt, J., Brinkmann, F., Longerich, T., Haag, G. M., et al. (2025) · Annals of Surgical Oncology · doi:10.1245/s10434-025-17233-9 · Cited by 8
“49,50 However, more research is currently needed to further explore these differences, and our study might contribute to more evidence in this field and the generation of hypotheses.”
Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation
Li, J., Xu, N., Hu, L., Xu, J., Huang, Y., Wang, D., Chen, F., Wang, Y., Jiang, J., Hong, Y., et al. (2025) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-025-04071-7 · Cited by 7
“We then used signatures summarized by Zeng et al. for tumor microenvironment characterization [57].”
Deciphering the dual role of autophagy in gastric cancer and gastroesophageal junction cancer: from tumor suppression to cancer progression
Lei, L., Zhang, J., Wei, R., Dong, B., Wang, X., & Zhou, Y. (2025) · Discover Oncology · doi:10.1007/s12672-025-02802-x · Cited by 8
Self-citation
Comprehensive analysis of the tumor immune microenvironment in gastric cancer and peritoneal metastasis based on single-cell RNA sequencing analysis
Sun, W., Jiang, Z., & Deng, Z. (2025) · Scientific Reports · doi:10.1038/s41598-025-13892-6 · Cited by 7
Comparative profiling of immune genes improves the prognoses of lower grade gliomas
Wang, Z., Cheng, W., Zhao, Z., Wang, Z., Zhang, C., Li, G., Wu, A., & Jiang, T. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2021.0173 · Cited by 7
Analysis of N6-Methyladenosine RNA Methylation Regulators in Diagnosis and Distinct Molecular Subtypes of Ankylosing Spondylitis
Zhong, C., Liang, J., Chen, Z., Zhong, L.-P., Sun, G., Xie, W., Wang, D.-P., Zhuang, W.-D., Guo, H.-H., Jin, D., et al. (2022) · Disease Markers · doi:10.1155/2022/4942599 · Cited by 7
“The process consists of two steps: the first step is to distinguish the m6A patterns; the second step is to calculate the m6A score according to the following formula [26, 27]: m6 Ascore =∑ðPC1i + PC2iÞ, where “i” represents DEG expression.”
Method
Up-Frameshift Suppressor 3 as a prognostic biomarker and correlated with immune infiltrates: A pan-cancer analysis
Xu, J., Ma, H., & Shan, B. (2022) · PLoS ONE · doi:10.1371/journal.pone.0273163 · Cited by 7
“To investigate the clinical predictive value of UPF3B for cancer immunotherapy, we calculated 15 TME scores which have a close association with immunotherapeutic outcomes [12].”
Method
Investigation on the regulatory T cells signature and relevant Foxp3/ STAT3 axis in esophageal cancer
Yang, L., Zhao, Q., Wang, X., Pilapong, C., Li, Y., Zou, J., Jin, J., & Rong, J. (2022) · Cancer Medicine · doi:10.1002/cam4.5194 · Cited by 7
Characterization of immune microenvironment infiltration and m6A regulator-mediated RNA methylation modification patterns in osteoarthritis
Ouyang, Y., Tu, Y., Chen, S., Min, H., Wen, Z., Zheng, G., Wan, T., Fan, H., Yang, W., & Sun, G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1018701 · Cited by 7
“The calculation method for determining the m(6)A gene signature score was based on previous studies (m(6)Ascore =∑ (PC1i + PC2i), i = the expression of m (6)A phenotypic related genes) (33, 34).”
Method
Systematic analysis of the cuprotosis in tumor microenvironment and prognosis of gastric cancer
Wang, K.-W., Wang, M.-D., Li, Z.-X., Hu, B.-S., Huang, J., Wu, J.-J., Yuan, Z.-D., Wu, X., Yuan, Q.-F., Sun, Y.-F., et al. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e13831 · Cited by 7
Comprehensive analysis of the basement membrane in lung adenocarcinoma by bulk and single-cell sequencing analysis
Shi, H., Sun, L. D., & Liu, B. (2023) · Journal of Cancer · doi:10.7150/jca.83407 · Cited by 7
“Apart from the expression of immune checkpoint inhibitors (ICIs: PD-1, PD-L1, Journal of Cancer 2023, Vol. 14 https://www.jcancer.org 1637 CTLA4, HAVCR2, LAG3, TIGIT) [13, 14], the tumour mutation burden (TMB) and T-cell receptor (TCR) repertoire were also found to predict immunotherapy efficiency [15, 16].”
Background
Coordination of Single-cell and Bulk RNA Sequencing to Construct a Cuproptosis-related Gene Prognostic Index for Endometrial Cancer Prognosis, Immune Microenvironment Infiltration, and Immunotherapy Treatment Options
Pang, X., Li, F., Lu, M., & Zhu, L. (2023) · Journal of Cancer · doi:10.7150/jca.86325 · Cited by 7
“…pembrolizumab (GSE78220 [24]), patients with advanced clear cell renal cell carcinoma treated with anti-PD-1 Nivolumab and anti-mTOR inhibitor everolimus (CheckMate025 [25]) were downloaded and analyzed to evaluate response of immunotherapy and determine the predictive value of the CRGPI [26].”
Method
A comprehensive pan-cancer analysis identifies a novel glycolysis score and its hub genes as prognostic and immunological biomarkers
Zheng, D., Long, S., & Xi, M. (2023) · Translational Cancer Research · doi:10.21037/tcr-23-325 · Cited by 7
Bidirectional crosstalk between the epithelial-mesenchymal transition and immunotherapy: A bibliometric study
Du, W., Tang, Z., Du, A., Yang, Q., & Xu, R. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2328403 · Cited by 7
Pan-cancer prognosis, immune infiltration, and drug resistance characterization of lung squamous cell carcinoma tumor microenvironment-related genes
Cheng, X. J., Li, R., Yin, Y., Liu, X., Zhou, X., & Qu, Y.-Q. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101722 · Cited by 7
Integrative analysis of aging-related genes reveals CEBPA as a novel therapeutic target in non-small cell lung cancer
Zhu, J., Zhu, X., Shi, C., Li, Q., Jiang, Y., Chen, X., Sun, P., Jin, Y., Wang, T., & Chen, J. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03457-4 · Cited by 7
“The tumor immune microenvironment (TIME) is critical in cancer development [21, 22].”
Background
Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals MMP mediated expression patterns by distinct tumor microenvironment immune profiles in cervical cancer
Wang, H., Li, X., Zhou, S., Guo, W., Wang, Z., Sun, L., Zhao, Z., Han, Y., Zhang, S., Lv, J., et al. (2024) · Journal of Cancer · doi:10.7150/jca.96429 · Cited by 7
“Similarly to the Gene Global Index (GGI) method, we defined the MMPscore [33, 34].”
Method
Tumor microenvironment assessment-based signatures for predicting response to immunotherapy in non-small cell lung cancer
Wu, J., Wang, Y., Huang, Z., Wu, J., Sun, H., Zhou, R., Qiu, W., Ye, Z., Fang, Y., Huang, X., et al. (2024) · iScience · doi:10.1016/j.isci.2024.111340 · Cited by 7
“18,19 Recently, we developed a tumor microenvironment score (TMEscore) that predicted ICBs responses with high accuracy 20 and integrated the TMEscore with a NanoString RNA panel for convenient clinical translation.”
Self-citation

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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