鉴定新的血浆蛋白作为良性前列腺增生的潜在治疗靶点:一项全蛋白质组关联研究。

IF 1.7 3区 医学 Q4 ANDROLOGY
Translational andrology and urology Pub Date : 2025-06-30 Epub Date: 2025-06-23 DOI:10.21037/tau-2025-187
Xinyi Luo, Changjing Wu, Yang Xiong, Wei Wang, Qing Jiang, Zhihong Liu
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引用次数: 0

摘要

背景:良性前列腺增生(BPH)是一种普遍存在的年龄相关疾病,其药物治疗效果不佳。为了系统地确定与BPH发病机制和治疗潜力相关的血浆蛋白,我们进行了一项结合多组学分析方法的蛋白质组关联研究(PWAS)。方法:利用全基因组关联研究(GWAS)的多性状分析(MTAG)对生物可利用睾酮(BAT)和BPH的GWAS数据集进行协调,提高发现能力。随后的蛋白质组学整合包括PWAS、两样本孟德尔随机化(MR)和贝叶斯共定位分析,并辅以途径富集评估。使用常规BPH GWAS数据进行验证。结果:这项综合分析确定了25种血浆蛋白与BPH风险显著相关(调整后的PWAS)结论:这是BPH的首次PWAS研究,描绘了一组具有机制和治疗意义的循环蛋白,特别强调了AIF1和RSPO3是功能验证和药物开发的优先候选蛋白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of novel plasma proteins as potential therapeutic targets for benign prostatic hyperplasia: a proteome-wide association study.

Background: Benign prostatic hyperplasia (BPH) represents a prevalent age-related disorder with suboptimal pharmacological management. To systematically identify plasma proteins causally linked to BPH pathogenesis and therapeutic potential, we conducted a proteome-wide association study (PWAS) integrated with multi-omics analytical approaches.

Methods: Genome-wide association study (GWAS) datasets of bioavailable testosterone (BAT) and BPH were harmonized by multi-trait analysis of GWAS (MTAG) to enhance discovery power. Subsequent proteomic integration encompassed PWAS, two-sample Mendelian randomization (MR), and Bayesian colocalization analyses, complemented by pathway enrichment evaluation. Validation was performed using conventional BPH GWAS data.

Results: This integrative analysis identified 25 plasma proteins exhibiting significant associations with BPH risk (adjusted P<0.05), including two proteins (AIF1 and RSPO3) independently validated in the conventional BPH GWAS dataset. MR analyses established causal relationships for 18 proteins (adjusted P<0.05), with Bayesian colocalization confirming shared causal variants between BPH and key proteins AIF1 [posterior probability 4 (PP4) =0.999], RSPO3 (PP4 =0.714), and COL2A1 (PP4 =0.920). Pathway analysis revealed enrichment in inflammatory signaling and extracellular matrix remodeling.

Conclusions: This first PWAS investigation of BPH delineates a panel of circulating proteins with mechanistic and therapeutic implications, particularly highlighting AIF1 and RSPO3 as priority candidates for functional validation and drug development.

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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
80
期刊介绍: ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.
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