Zhou Wenjie, Ding Jiawei, Shen Yan, Huang Fanyu, Xu Danfeng
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Research Center for Experimental Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Medicine (Baltimore). 2025 Sep 5;104(36):e44282. doi: 10.1097/MD.0000000000044282.
Prior research suggested the potential correlation between circulating immune cell phenotypes and prostate cancer (PCa). However, it remains unclear whether the correlation can be mediated by plasma metabolites. We performed a bidirectional 2-sample, 2-step Mendelian randomization (MR) study mainly utilizing the inverse variance weighted method to examine the causal role of circulating immunophenotypes on PCa and explore the mediation effect of plasma metabolites in the pathway from immunophenotypes to PCa. MR analyses revealed that 7 circulating immune cell phenotypes and 9 plasma metabolites were significantly related to the risk of PCa. Notably, the mediation MR analysis revealed that X-12100 levels accounted for 10.5% of the decreased risk of PCa associated with CD4 + CD8dim AC in TBNK panel, and X-24418 levels accounted for 11.8% of the elevated risk of PCa related to FSC-A on granulocyte in cDC panel. Our study established a causal relationship between immunophenotypes and PCa, and unveiled the mediating role of plasma metabolites in this association. Meanwhile, we emphasized the notable impact of the immune-metabolite axis on PCa, and immune cells may promote or inhibit tumor progression by influencing metabolite levels, providing a novel insight for studying the pathogenic mechanisms of PCa.
先前的研究表明循环免疫细胞表型与前列腺癌（PCa）之间存在潜在关联。然而，这种关联是否可由血浆代谢物介导仍不清楚。我们进行了一项双向双样本两步孟德尔随机化（MR）研究，主要采用逆方差加权法来检验循环免疫表型对PCa的因果作用，并探索血浆代谢物在从免疫表型到PCa的通路中的中介作用。MR分析显示，7种循环免疫细胞表型和9种血浆代谢物与PCa风险显著相关。值得注意的是，中介MR分析显示，在TBNK组中，X-12100水平占与CD4 + CD8dim AC相关的PCa风险降低的10.5%，在cDC组中，X-24418水平占与粒细胞上FSC-A相关的PCa风险升高的11.8%。我们的研究建立了免疫表型与PCa之间的因果关系，并揭示了血浆代谢物在这种关联中的中介作用。同时，我们强调了免疫-代谢轴对PCa具有显著影响，免疫细胞可能通过影响代谢物水平促进或抑制肿瘤进展，为研究PCa的致病机制提供了新的见解。
