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Meta-Analysis
. 2024 Dec;73(12):2141-2152.
doi: 10.1007/s00011-024-01955-9. Epub 2024 Oct 1.

Immune cells mediate the causal pathway linking circulating complements to cancer: A Mendelian randomization study

Hao Pan  1 , Changqing Jing  2   3
Affiliations
Meta-Analysis

Immune cells mediate the causal pathway linking circulating complements to cancer: A Mendelian randomization study

Hao Pan et al. Inflamm Res. 2024 Dec.

Abstract

Background: The role of complement in cancer remains controversial. Whether immune cells and inflammatory factors mediate the pathway from complement to cancer has not been fully elucidated.

Methods: We conducted bidirectional Mendelian randomization (MR) analysis to explore the causal association between complement components and cancer. Meta-analysis was conducted to enhance the robustness of the results. We further explored the mediation roles of immune cells and inflammatory factors in these associations.

Results: Our study identified causal associations between 11 complement components and 12 types of cancer. Furthermore, we identified five immune cells as potential mediators: BAFF-R on IgD + CD38- naive B cell mediated 7.434% of the increased risk for liver cancer from C3; CD4 on CD39 + activated CD4 regulatory T cell mediated 12.384% of the increased risk for biliary tract cancer from CD93; CD25 + + CD45RA + CD4 not regulatory T cell and Basophil %CD33dim HLA DR- CD66b- mediated 7.721% and 7.986% of the increased risk of colorectal cancer from MASP1, respectively; CD45RA on resting CD4 regulatory T cell mediated 11.444% of the increased risk of skin cancer from MASP1.

Conclusion: This study revealed the causal relationships between complement components and certain cancers, with five immune cells as potential mediators.

Keywords: Cancer; Complement components; Immune cells; Inflammatory factor; Mendelian randomization.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and informed consent. Ethical approval was not applicable because this study used data from publicly available databases. Consent for publication: Not application.

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