Cong Zhicheng, Qiu Dandan, Hu Haiping
Department of Urology, Zhejiang Hospital, Hangzhou, Zhejiang, China.
Department of Urology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Medicine (Baltimore). 2025 Aug 1;104(31):e43613. doi: 10.1097/MD.0000000000043613.
Prostate cancer (PCa) lacks precise diagnostic tools, necessitating noninvasive biomarkers. MicroRNAs (miRNAs) show promise due to fluid stability and oncogenic regulation. Using 2-sample Mendelian randomization (MR), we analyzed plasma miRNA expression quantitative trait loci (eQTLs) from discovery and validation cohorts. Cis-acting eQTLs served as instrumental variables, with causal effects assessed via inverse-variance weighted (IVW) and MR-Egger regression. Functional and survival analyses leveraged The Cancer Genome Atlas (TCGA)-PRAD data and bioinformatics tools. Five miRNAs (hsa-miR-127-3p, -370-3p, -125a-5p, -433-3p, -99b-5p) were inversely associated with PCa risk (IVW P < .05, FDR < 0.1). Two (hsa-miR-125a-5p/-99b-5p) were validated (OR = 0.992-0.9924, P < .05). Their 553 target genes included 9 survival-linked genes (e.g., FOXM1, BTG2), enriched in basement membrane organization, glutathione metabolism, and senescence. hsa-miR-127-3p was downregulated in PCa (fold change = 0.7, P < .001), with pan-cancer prognostic relevance. hsa-miR-125a-5p and -99b-5p are causal protective factors against PCa, modulating oncogenic pathways and survival. These miRNAs offer potential as noninvasive biomarkers and therapeutic targets, advancing precision oncology.
前列腺癌（PCa）缺乏精确的诊断工具，因此需要非侵入性生物标志物。由于在体液中稳定性良好且具有致癌调节作用，微小RNA（miRNA）显示出应用前景。我们使用两样本孟德尔随机化（MR）方法，分析了来自发现队列和验证队列的血浆miRNA表达定量性状位点（eQTL）。顺式作用eQTL用作工具变量，通过逆方差加权（IVW）和MR-Egger回归评估因果效应。功能和生存分析利用了癌症基因组图谱（TCGA）-PRAD数据和生物信息学工具。5种miRNA（hsa-miR-127-3p、-370-3p、-125a-5p、-433-3p、-99b-5p）与PCa风险呈负相关（IVW P < 0.05，FDR < 0.1）。其中两种（hsa-miR-125a-5p/-99b-5p）得到验证（OR = 0.992 - 0.9924，P < 0.05）。它们的553个靶基因包括9个与生存相关的基因（如FOXM1、BTG2），这些基因在基底膜组织、谷胱甘肽代谢和衰老过程中富集。hsa-miR-127-3p在PCa中表达下调（倍数变化 = 0.7，P < 0.001），具有泛癌预后相关性。hsa-miR-125a-5p和-99b-5p是PCa的因果保护因子，可调节致癌途径和生存。这些miRNA有望成为非侵入性生物标志物和治疗靶点，推动精准肿瘤学发展。
