Pan Hao, Jing Changqing
Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, Shandong, People's Republic of China.
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China.
Inflamm Res. 2024 Dec;73(12):2141-2152. doi: 10.1007/s00011-024-01955-9. Epub 2024 Oct 1.
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.
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.
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.
This study revealed the causal relationships between complement components and certain cancers, with five immune cells as potential mediators.
补体在癌症中的作用仍存在争议。免疫细胞和炎症因子是否介导了从补体到癌症的通路尚未完全阐明。
我们进行了双向孟德尔随机化（MR）分析，以探索补体成分与癌症之间的因果关联。进行荟萃分析以增强结果的稳健性。我们进一步探讨了免疫细胞和炎症因子在这些关联中的中介作用。
我们的研究确定了11种补体成分与12种癌症之间的因果关联。此外，我们确定了五种免疫细胞作为潜在的中介：IgD + CD38 - 幼稚B细胞上的BAFF - R介导了C3导致的肝癌风险增加的7.434%；CD39 + 活化的CD4调节性T细胞上的CD4介导了CD93导致的胆管癌风险增加的12.384%；CD25 ++ CD45RA + CD4非调节性T细胞和嗜碱性粒细胞%CD33dim HLA DR - CD66b - 分别介导了MASP1导致的结直肠癌风险增加的7.721%和7.986%；静息CD4调节性T细胞上的CD45RA介导了MASP1导致的皮肤癌风险增加的11.444%。
本研究揭示了补体成分与某些癌症之间的因果关系，其中五种免疫细胞为潜在中介。
