Wang Zhengshi, Chen Haotian, Liu Yongqiang, Zou Libin, Zhang Zhijin, Yin Zhiqiang, Mao Shiyu, Guo Changcheng, Yang Bin, Wu Pengfei, Yao Xudong
Department of Urology, Shanghai Tenth People's Hospital, Clinical Medical College of Nanjing Medical University, Shanghai, China.
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Oncol. 2025 Jan 15;14:1466190. doi: 10.3389/fonc.2024.1466190. eCollection 2024.
Studies have shown that gut microbiota is involved in the tumorigenesis and development of prostate cancer. We aimed to perform a comprehensive analysis of causal associations of gut microbiota, metabolites, and cytokines with prostate cancer in the Asian population.
Genome-wide association study (GWAS) summary datasets were collected from the public databases. There were 418 bacterial traits, 452 metabolites, 91 cytokines, 5408 cases of prostate cancer from East Asia, and 109,347 controls included. Mendelian randomization (MR) analyses were performed to investigate their causal relationships. Sensitivity analyses were conducted to test the reliability of MR results. Furthermore, the FinnGen database was used to assess the generalizability of our findings based on Asians.
There were a total of 17 bacterial traits, 28 metabolites (including 2 microbiota-associated metabolites), and 9 cytokines to be significantly associated with prostate cancer in Asians (P < 0.05). Further MR analyses of these positive results indicated that /TNFSF10 axis, /TNFRSF14 axis, /TNFSF10 axis, and P_Proteobacteria/cholesterol axis were key signaling pathways involved in the progression of prostate cancer. Notably, /TNFSF10 axis and /TNFRSF14 axis were found to act as protective factors, while the other two signaling axes played a crucial role in promoting the progression of prostate cancer. Sensitivity analyses further confirmed the reliability of our findings. Using the European population as outcome, we further assessed the generalizability of our conclusions and found limited applicability to Europeans.
We found that there were causal associations of gut microbiota, metabolites, and cytokines with prostate cancer in Asians. The causal effects of gut microbiota on prostate cancer were partially mediated by metabolites and cytokines. These findings might contribute to the development of new therapeutic strategies for prostate cancer.
研究表明肠道微生物群参与前列腺癌的发生和发展。我们旨在对亚洲人群中肠道微生物群、代谢物和细胞因子与前列腺癌的因果关联进行全面分析。
从公共数据库收集全基因组关联研究（GWAS）汇总数据集。纳入了418个细菌特征、452种代谢物、91种细胞因子、来自东亚的5408例前列腺癌病例以及109347名对照。进行孟德尔随机化（MR）分析以研究它们之间的因果关系。进行敏感性分析以检验MR结果的可靠性。此外，使用芬兰基因组数据库（FinnGen database）基于亚洲人评估我们研究结果的普遍性。
在亚洲人中，共有17个细菌特征、28种代谢物（包括2种与微生物群相关的代谢物）和9种细胞因子与前列腺癌显著相关（P < 0.05）。对这些阳性结果进一步进行MR分析表明，/TNFSF10轴、/TNFRSF14轴、/TNFSF10轴和P_变形菌门/胆固醇轴是参与前列腺癌进展的关键信号通路。值得注意的是，/TNFSF10轴和/TNFRSF14轴被发现起到保护作用，而其他两个信号轴在促进前列腺癌进展中起关键作用。敏感性分析进一步证实了我们研究结果的可靠性。以欧洲人群作为结果，我们进一步评估了我们结论的普遍性，发现对欧洲人的适用性有限。
我们发现在亚洲人中肠道微生物群、代谢物和细胞因子与前列腺癌存在因果关联。肠道微生物群对前列腺癌的因果效应部分由代谢物和细胞因子介导。这些发现可能有助于开发前列腺癌的新治疗策略。
