ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1609933
This article is part of the Research TopicIntegrating Genetics and Proteomics for Drug DiscoveryView all 3 articles
Multi-omic Insights into Mitochondrial Dysfunction and Prostatic Disease: Evidence from Transcriptomics, Proteomics, and Methylomics
Provisionally accepted
Binbin Gong*
Feixiang Yang
Ning Zhang
Zhengyang WuKun Wang
Kun WangXiangyu ZhangYangyang ZhangZhengyao Song
Chaozhao Liang- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, China
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Background: Prostatic diseases, consisting of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa), pose significant health challenges. While single-omics studies have provided valuable insights into the role of mitochondrial dysfunction in prostatic diseases, integrating multi-omics approaches is essential for uncovering disease mechanisms and identifying therapeutic targets. Methods: A genome-wide meta-analysis was conducted for prostatic diseases using the genome-wide association studies (GWAS) data from FinnGen and UK Biobank. Mitochondrial dysfunction-related genes were reviewed based on MitoCarta 3.0, with a library containing 1,244 mitochondrial genes. We integrated multi-omics through quantitative trait loci (QTL) across gene expression (eQTLs), protein abundance (pQTLs), and DNA methylation (mQTLs). We prioritized prostatic disease-related mitochondrial genes into three confidence tiers: Tier 1 (two eQTLs + pQTL + mQTL); Tier 2 (two eQTLs + pQTL/mQTL); and Tier 3 (eQTL + pQTL/mQTL). Further mediation analyses were performed to explore potential mediating pathways for the interaction between mitochondrial dysfunction and prostatic diseases, with 1400 metabolomics and 731 immunomics. Results: We identified DCXR as the gene with Tier 1 evidence for BPH, validated by multi-omics integration through transcriptomic, proteomic, and methylomic signatures. We revealed two Tier 2 genes (NOA1 and ELAC2) and one Tier 3 gene (ACAT1) for BPH, two Tier 3 genes (TRMU and SFXN5) for prostatitis, and six Tier 3 genes (MRPL24, NDUFS6, PUS1, NBR1, GLOD4, and PCBD2) for PCa. We also explored the mediating pathways of mitochondrial genes (within the 3-tiers evidence) on prostatic diseases, and identified 8, 4, and 13 metabolites mediating the interaction between mitochondrial genes and BPH, prostatitis, and PCa, respectively, without the involvement of immune characters. Conclusion: These findings highlight the roles of mitochondrial dysfunction-related genes in prostatic diseases and identify key genes and pathways for potential therapeutic targets.
Keywords: Mitochondrial dysfunction, multi-omics, Prostatitis, Benign prostatic hyperplasia, prostate cancer
Received: 15 Apr 2025; Accepted: 09 Jul 2025.
Copyright: © 2025 Gong, Yang, Zhang, Wu, Wang, Wang, Zhang, Zhang, Song and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Binbin Gong, Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, China
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