{"doi":"10.1002/mc.23828","title":"Integrating Multi‐Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk‐associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (<jats:italic>N</jats:italic> = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. We observed significant associations for 3879 CpG sites, including 926 at novel genomic loci. Among them, DNAm levels of 80 CpG sites located at novel loci are significantly associated with expression levels of 45 neighboring genes in normal prostate tissue. Of these genes, 11 further exhibit significant associations with PCa risk for their predicted expression levels in prostate tissue. Intriguingly, a total of 31 CpG sites demonstrate consistent association patterns across the methylation–gene expression–PCa risk pathway. Our findings suggest that specific CpG sites may be related to PCa risk by modulating the expression of nearby target genes.</jats:p>","journal":"Molecular Carcinogenesis","year":2025,"id":593860,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1403304,"name":"Jingjing Zhu","orcid":"0000-0002-9762-8480","position":1,"is_corresponding":false},{"id":903831,"name":"Dylan Green","orcid":"0000-0003-3938-8527","position":2,"is_corresponding":false},{"id":208636,"name":"Hua Zhong","orcid":"0000-0002-9358-1582","position":3,"is_corresponding":false},{"id":27519,"name":"Quan Long","orcid":"0000-0003-3795-1873","position":4,"is_corresponding":false},{"id":943377,"name":"Chong Wu","orcid":"0009-0006-7007-9692","position":5,"is_corresponding":false},{"id":291508,"name":"Lei Wang","orcid":"0000-0002-9364-8572","position":6,"is_corresponding":false},{"id":320407,"name":"Youping Deng","orcid":"0000-0002-5951-8213","position":7,"is_corresponding":false},{"id":240062,"name":"Lang Wu","orcid":"0000-0001-9938-3627","position":8,"is_corresponding":false},{"id":992659,"name":"Shuai Liu","orcid":"0000-0003-2244-2216","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Integrating Multi‐Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk‐associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (<jats:italic>N</jats:italic> = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. We observed significant associations for 3879 CpG sites, including 926 at novel genomic loci. Among them, DNAm levels of 80 CpG sites located at novel loci are significantly associated with expression levels of 45 neighboring genes in normal prostate tissue. Of these genes, 11 further exhibit significant associations with PCa risk for their predicted expression levels in prostate tissue. Intriguingly, a total of 31 CpG sites demonstrate consistent association patterns across the methylation–gene expression–PCa risk pathway. Our findings suggest that specific CpG sites may be related to PCa risk by modulating the expression of nearby target genes.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39400371","pmcid":"PMC12009774","openalex_id":"https://openalex.org/W4403396935","authors":[],"funders":[{"funder_name":"NHGRI NIH HHS","grant_id":"U54 HG013243","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA263494","title":null},{"funder_name":"This study is supported by the University of Hawai'i Cancer Center, NCI R01 CA263494 (National Cancer Institute), and NHGRI/NIMHD U54 HG013243 (National Human Genome Research Institute).","grant_id":"","title":null},{"funder_name":"This study is supported by the University of Hawai'i Cancer Center, NCI R01 CA263494 (National Cancer Institute), and NHGRI/NIMHD U54 HG013243 (National Human Genome Research Institute).","grant_id":"","title":null}],"total_grants":4,"fwci":0.3732,"citation_percentile":0.61338884,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mc.23828","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mc.23828","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/mc.23828","host_type":"publisher"},{"url":"https://doi.org/10.1002/mc.23828","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39400371","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12009774/","host_type":"repository"},{"url":"https://digitalcommons.library.tmc.edu/uthgsbs_docs/6807","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12009774","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12009774/pdf/nihms-2069084.pdf","host_type":"repository"}],"fields_of_study":["Epigenetics and DNA Methylation","Prostate Cancer Treatment and Research","Genetic Associations and Epidemiology","Humans","Male","Prostatic Neoplasms","DNA Methylation","CpG Islands","Biomarkers, Tumor","Prostate","Gene Expression Regulation, Neoplastic","Case-Control Studies","Genetic Predisposition to Disease","Genomics","Risk Factors","Multiomics"],"mesh_terms":["Multiomics","Humans","Male","Prostate","Prostatic Neoplasms","Risk Factors","Biomarkers, Tumor","Gene Expression Regulation, Neoplastic","Case-Control Studies","CpG Islands","DNA Methylation","Genetic Predisposition to Disease","Genomics"],"keywords":["Prostate cancer","dNaM","Biology","CpG site","DNA methylation","Prostate","Gene","Methylation","Computational biology","Genetics","Gene expression","Cancer","Association"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T12:32:57.318706Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}