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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Diisononyl cyclohexane-1,2-dicarboxylate (DINCH), a non-phthalate plasticizer adopted as a safer alternative for food-contact and medical-grade materials, is ubiquitously detected in human biomonitoring studies. Despite widespread exposure, its transcriptional effects in prostate cells and the potential prostate cancer relevance of DINCH-responsive genes remain unclear. We integrated transcriptomic profiling of DINCH-exposed human prostate epithelial cells with exploratory genetic association analyses in 630 patients with prostate cancer receiving androgen deprivation therapy (ADT). Haplotype-tagged single-nucleotide polymorphisms (SNPs) in candidate DINCH-responsive genes were evaluated for their association with overall survival (OS) and cancer-specific survival (CSS). The prostate cancer relevance of the prioritized genes was further validated using pooled multi-cohort bioinformatic analyses. DINCH exposure produced an exploratory molecular signature comprising 83 genes across all tested doses, broadly suppressing cell\u2013matrix adhesion pathways and activating chromatin remodeling. Exploratory genetic screening identified nominal associations of LPP rs1040033 with OS (p = 0.0002, q = 0.131) and FAM111B rs7110278 with CSS (p = 0.0010, q = 0.575); neither association remained significant after multiple-testing correction. DINCH exposure significantly downregulated LPP and upregulated FAM111B expression in prostate epithelial cells. Independently, pooled analyses demonstrated reduced LPP and elevated FAM111B expression in prostate cancer tissues compared with normal prostate tissues. Higher LPP expression predicted a favorable prognosis, whereas elevated FAM111B predicted worse survival. Pathway analyses linked low LPP expression to impaired adhesion signaling and metabolic reprogramming, whereas high FAM111B expression was associated with mitotic and cell-cycle activation. DINCH exposure induced exploratory transcriptional alterations involving LPP-related adhesion pathways and FAM111B-related proliferative signaling. The genetic findings are exploratory and require independent validation. Although public datasets support the prognostic relevance of LPP and FAM111B in prostate cancer, they do not link these genes to DINCH exposure.<\/jats:p>","DOI":"10.3390\/ijms27177686","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"7686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Toxicogenomic Profiling Identifies Candidate DINCH-Responsive Genes Relevant to Prostate Cancer"],"prefix":"10.3390","volume":"27","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-1626","authenticated-orcid":false,"given":"Wen-Hsin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, China Medical University, Taichung 406, 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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2620-1914","authenticated-orcid":false,"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 Chiao Tung 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 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\/0000-0001-5510-6513","authenticated-orcid":false,"given":"Bo-Ying","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hlisnikova, H., Petrovicova, I., Kolena, B., Sidlovska, M., and Sirotkin, A. 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