Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics
BackgroundProstatic 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-o...
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Frontiers Media S.A.
2025-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1609933/full |
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| author | Binbin Gong Binbin Gong Binbin Gong Feixiang Yang Feixiang Yang Feixiang Yang Ning Zhang Zhengyang Wu Tianrui Liu Kun Wang Xiangyu Zhang Yangyang Zhang Zhengyao Song Chaozhao Liang Chaozhao Liang Chaozhao Liang |
| author_facet | Binbin Gong Binbin Gong Binbin Gong Feixiang Yang Feixiang Yang Feixiang Yang Ning Zhang Zhengyang Wu Tianrui Liu Kun Wang Xiangyu Zhang Yangyang Zhang Zhengyao Song Chaozhao Liang Chaozhao Liang Chaozhao Liang |
| author_sort | Binbin Gong |
| collection | DOAJ |
| description | BackgroundProstatic 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.MethodsA 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 1,400 metabolomics and 731 immunomics.ResultsWe 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.ConclusionThese findings highlight the roles of mitochondrial dysfunction-related genes in prostatic diseases and identify key genes and pathways for potential therapeutic targets. |
| format | Article |
| id | doaj-art-d64b222fefbc4607b8fa697968870a3a |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-d64b222fefbc4607b8fa697968870a3a2025-08-22T04:10:35ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-08-011610.3389/fgene.2025.16099331609933Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomicsBinbin Gong0Binbin Gong1Binbin Gong2Feixiang Yang3Feixiang Yang4Feixiang Yang5Ning Zhang6Zhengyang Wu7Tianrui Liu8Kun Wang9Xiangyu Zhang10Yangyang Zhang11Zhengyao Song12Chaozhao Liang13Chaozhao Liang14Chaozhao Liang15Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaInstitute of Urology, Anhui Medical University, Hefei, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaInstitute of Urology, Anhui Medical University, Hefei, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaFirst School of Clinical Medicine, Anhui Medical University, Hefei, ChinaSecond School of Clinical Medicine, Anhui Medical University, Hefei, ChinaSecond School of Clinical Medicine, Anhui Medical University, Hefei, ChinaFirst School of Clinical Medicine, Anhui Medical University, Hefei, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaInstitute of Urology, Anhui Medical University, Hefei, ChinaAnhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, ChinaBackgroundProstatic 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.MethodsA 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 1,400 metabolomics and 731 immunomics.ResultsWe 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.ConclusionThese findings highlight the roles of mitochondrial dysfunction-related genes in prostatic diseases and identify key genes and pathways for potential therapeutic targets.https://www.frontiersin.org/articles/10.3389/fgene.2025.1609933/fullmitochondrial dysfunctionmulti-omicsprostatitisbenign prostatic hyperplasiaprostate cancer |
| spellingShingle | Binbin Gong Binbin Gong Binbin Gong Feixiang Yang Feixiang Yang Feixiang Yang Ning Zhang Zhengyang Wu Tianrui Liu Kun Wang Xiangyu Zhang Yangyang Zhang Zhengyao Song Chaozhao Liang Chaozhao Liang Chaozhao Liang Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics Frontiers in Genetics mitochondrial dysfunction multi-omics prostatitis benign prostatic hyperplasia prostate cancer |
| title | Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics |
| title_full | Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics |
| title_fullStr | Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics |
| title_full_unstemmed | Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics |
| title_short | Multi-omic insights into mitochondrial dysfunction and prostatic disease: evidence from transcriptomics, proteomics, and methylomics |
| title_sort | multi omic insights into mitochondrial dysfunction and prostatic disease evidence from transcriptomics proteomics and methylomics |
| topic | mitochondrial dysfunction multi-omics prostatitis benign prostatic hyperplasia prostate cancer |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1609933/full |
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