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Medical University","doi-asserted-by":"crossref","award":["CMU113-TC-04"],"award-info":[{"award-number":["CMU113-TC-04"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"crossref","award":["CMU113-MF-11"],"award-info":[{"award-number":["CMU113-MF-11"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007300","name":"China Medical University","doi-asserted-by":"crossref","award":["CMU114-MF-80"],"award-info":[{"award-number":["CMU114-MF-80"]}],"id":[{"id":"10.13039\/501100007300","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objective: Di-2-ethylhexyl phthalate and its bioactive metabolite mono-2-ethylhexyl phthalate (MEHP) are ubiquitous endocrine-disrupting chemicals implicated in carcinogenesis. However, the molecular mechanisms linking MEHP exposure, host genetic susceptibility, and prostate cancer progression remain incompletely defined. Methods: We integrated transcriptomic profiling of MEHP-exposed human prostate epithelial cells with a genetic association study of 630 patients with prostate cancer receiving androgen deprivation therapy. MEHP-responsive genes were identified from public microarray datasets and subjected to pathway enrichment analyses. Germline single-nucleotide polymorphisms (SNPs) in MEHP-regulated genes were evaluated for their association with progression-free survival, overall survival, and cancer-specific survival. The clinical and functional relevance of the key genes was further assessed using large-scale public prostate cancer expression datasets. Results: MEHP exposure induced widespread transcriptional reprogramming, prominently suppressing focal adhesion and cell\u2013matrix interaction pathways. Genetic analyses identified multiple prognostically relevant SNPs within MEHP-responsive genes, with anoctamin 4 (ANO4) variants showing consistent associations across all clinical endpoints. The minor allele of rs17485225 in ANO4 was significantly associated with reduced all-cause and prostate cancer-specific mortality. Pooled analyses revealed reduced ANO4 expression levels in prostate cancer tissues and improved survival in patients with high ANO4 expression levels. Pathway analyses linked low ANO4 expression levels with enhanced cell cycle activity and compromised cell adhesion. Conclusions: Our findings suggest that ANO4 may act as a mediator of MEHP-associated prostate cancer progression and support a gene\u2013environment interaction model in which environmental toxicant exposure and germline variation converge on focal adhesion dysregulation to potentially contribute to aggressive disease.<\/jats:p>","DOI":"10.3390\/diagnostics16050794","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:27:18Z","timestamp":1773062838000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Plastics to Prognosis: ANO4 Susceptibility Links Phthalate Exposure to Prostate Cancer Progression"],"prefix":"10.3390","volume":"16","author":[{"given":"Chi-Fen","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Pin","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan"},{"name":"Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan"},{"name":"Institute of Medical Science and Technology, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3891-5172","authenticated-orcid":false,"given":"Yei-Tsung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lih-Chyang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Cheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"},{"name":"Department of Urology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan"},{"name":"Department of Pharmacy, College of Pharmacy and Health Care, Tajen University, Pingtung 907, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology, E-Da Hospital, Kaohsiung 824, Taiwan"},{"name":"School of Medicine for International Students, I-Shou University, Kaohsiung 840, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1408-6004","authenticated-orcid":false,"given":"Te-Ling","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-6513","authenticated-orcid":false,"given":"Bo-Ying","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1289\/ehp.730395","article-title":"Extraction, localization, and metabolism of di-2-ethylhexyl phthalate from PVC plastic medical devices","volume":"3","author":"Jaeger","year":"1973","journal-title":"Environ. 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