Evidence map›Paper›PMID 41305837›Full record

ArticleMedicine2025

CD5 mediates the link between CD4+ CD39+ activated Treg cells and gastric cancer: A Mendelian randomization study.

Qiao Zhang, Xuezhi Zhou, Sai Cheng, Xinjun Wu, Dezhong Zhang, Shaohui Zhu

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In one paragraph

Article in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Qiao ZhangDepartment of Gastrointestinal Weight Loss Metabolism and Hernia Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City, Henan Province, China.ORCID 0009-0009-1291-8349
Xuezhi ZhouCollege of Medical Engineering, Xinxiang Medical University, Xinxiang City, Henan Province, China.
Sai ChengDepartment of Dermatology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City, Henan Province, China.
Xinjun WuDepartment of Gastrointestinal Weight Loss Metabolism and Hernia Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City, Henan Province, China.
Dezhong ZhangDepartment of Gastrointestinal Weight Loss Metabolism and Hernia Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City, Henan Province, China.
Shaohui ZhuDepartment of Gastrointestinal Weight Loss Metabolism and Hernia Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang City, Henan Province, China.

Funding

the National Natural Science Foundation of China Grant No. 82302298
6 · The paper itself

Abstract

Gastric cancer (GC) remains one of the leading causes of cancer mortality worldwide. The tumor immune microenvironment plays a pivotal role in GC progression, with regulatory T cells (Tregs), particularly the CD4+ CD39+ subset, implicated in immune suppression. However, the causal role of CD4+ CD39+ Treg cells in GC remains unclear. Additionally, CD5, a T cell surface glycoprotein, may influence immune responses in cancer. This study aims to clarify the relationship between CD4+ CD39+ Treg cells and GC risk and explore the potential mediating role of CD5 using a Mendelian randomization (MR) approach. A bidirectional 2-sample MR analysis was conducted using genome-wide association study data. CD4+ CD39+ Treg cell data were sourced from the IEU genome-wide association study database (N = 2920), and GC data were retrieved from the FennGenn consortium (N = 2,88,444; 1307 cases, 2,87,137 controls). Analyses included inverse variance weighted, MR-Egger regression, weighted median, and Mendelian randomization-Pleiotropy RESidual Sum and Outlier to test robustness and pleiotropy. A 2-step MR was performed to evaluate the mediating role of CD5. Results indicated that increased CD4+ CD39+ Treg cell levels were associated with a reduced risk of GC (odds ratio [OR] = 0.907, 95% confidence interval [CI] = 0.829-0.993, P = .035). No heterogeneity or pleiotropy was observed, and reverse causality was excluded (OR = 0.983, 95% CI = 0.931-1.038, P = .530). Additionally, CD4+ CD39+ Treg cells influenced CD5 expression (OR = 0.970, 95% CI = 0.943-0.998, P = .035), and elevated CD5 levels were linked to increased GC risk (OR = 1.285, 95% CI = 1.030-1.603, P = .026). Mediation analysis revealed that CD5 accounted for 7.74% of the protective effect of CD4+ CD39+ Treg cells on GC. CD4+ CD39+ Treg cells are causally linked to a reduced risk of GC, with CD5 mediating a small but significant portion of this protective effect. These findings highlight the importance of immune regulation in GC and suggest that targeting CD5 could be a therapeutic strategy. Further research is needed to investigate additional mediators contributing to GC development.

Indexed as

ApyraseStomach NeoplasmsT-Lymphocytes, RegulatoryGenome-Wide Association StudyHumansMendelian Randomization AnalysisApyraseENTPD1 protein, humanCD4+ CD39+ Treg cellsCD5gastric cancerimmune mediationMendelian randomizationtumor microenvironment

Identifiers

PMID41305837
PMCPMC12643594

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.