Department of Urology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, ZhuZhou, People's Republic of China.
Department of Reproductive Medicine Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, ZhuZhou, People's Republic of China.
Sci Rep. 2024 Oct 31;14(1):26217. doi: 10.1038/s41598-024-78085-z.
Research has demonstrated the significant involvement of immune cells in the development and progression of prostate cancer (PCa). However, the precise causal relationship between immune cells and PCa remains unclear. This study utilized bidirectional Mendelian randomization (MR) analysis to investigate the causal link between immune cells and PCa. Additionally, employed mediation MR design to ascertain the potential mediating role of metabolites in the connection between immune cells and PCa outcomes. Unswitched memory B cell % lymphocyte and CD24 + CD27 + B cell % lymphocyte were positively related to PCa risk, while CD62L - monocyte absolute count and CD62L - monocyte % monocyte were negatively associated with PCa risk. Sensitivity analysis was conducted to validate these results. The mediation MR results indicate that 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) levels may be an independent risk factor for PCa, while the succinate to acetoacetate ratio (SA ratio) was found to be a mediator for the effect of CD62L - monocyte % monocyte on PCa, with a mediation proportion of 16.6% (mediation percentage: 16.6%, 95%CI - 163% - 196%). The research validates the genetic causality between particular immune cells and PCa, and has emphasized the potential intermediary function of SA ratio. These noteworthy discoveries provide fresh perspectives for the clinical management of PCa.
研究表明，免疫细胞在前列腺癌（PCa）的发生和发展中起着重要作用。然而，免疫细胞与 PCa 之间的确切因果关系仍不清楚。本研究采用双向孟德尔随机化（MR）分析来研究免疫细胞与 PCa 之间的因果关系。此外，还采用中介 MR 设计来确定代谢物在免疫细胞与 PCa 结局之间的潜在中介作用。未转换记忆 B 细胞%淋巴细胞和 CD24+CD27+B 细胞%淋巴细胞与 PCa 风险呈正相关，而 CD62L-单核细胞绝对计数和 CD62L-单核细胞%单核细胞与 PCa 风险呈负相关。进行了敏感性分析以验证这些结果。中介 MR 结果表明，3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）水平可能是 PCa 的一个独立危险因素，而琥珀酸与乙酰乙酸的比值（SA 比值）被发现是 CD62L-单核细胞%单核细胞对 PCa 影响的中介，中介比例为 16.6%（中介百分比：16.6%，95%CI -163%-196%）。该研究验证了特定免疫细胞与 PCa 之间的遗传因果关系，并强调了 SA 比值的潜在中介作用。这些有意义的发现为 PCa 的临床管理提供了新的视角。
