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Prostate cancer is one of the most common malignancies among men worldwide, and clinical outcomes following androgen deprivation therapy (ADT) vary considerably. Given that endoplasmic reticulum (ER) stress and the unfolded protein response mediate processes such as apoptosis, tumor adaptation, and disease progression, we aimed to investigate whether genetic variants in ER stress-related genes are associated with survival outcomes in patients with prostate cancer receiving ADT. Methods: This study enrolled 630 patients with prostate cancer who underwent ADT across three medical centers in Taiwan. A genetic association analysis of 89 haplotype-tagged single-nucleotide polymorphisms (SNPs) across 12 ER stress-related genes was performed. The primary clinical endpoint was overall survival (OS). Kaplan\u2013Meier survival analysis and Cox proportional hazards models were used to evaluate prognostic associations. Furthermore, publicly available databases were integrated to analyze gene expression, clinical relevance, gene set enrichment, and tumor immune infiltration to elucidate the underlying biological mechanisms. Results: Among the analyzed SNPs, BAX rs182509214 showed the strongest association with OS. The minor G allele of BAX rs182509214 was significantly associated with poorer OS. Prostate tumor tissues exhibited markedly elevated BAX expression compared with normal prostate tissues, and this elevated expression was associated with worse survival outcomes. Multiple public gene expression datasets confirmed the overexpression of BAX in prostate cancer. Functional analyses revealed that genes associated with BAX expression were predominantly enriched in ribosomal, oxidative phosphorylation, and proteasomal pathways. Furthermore, the BAX copy number variation was significantly associated with the infiltration levels of multiple immune cell types, and BAX expression was negatively correlated with CD8+ T-cell infiltration, implying a potential marker role for the tumor immune microenvironment. Conclusions: The ER stress-related genetic variant, BAX rs182509214, may influence survival outcomes in patients with prostate cancer receiving ADT. BAX alterations are associated with disease progression and linked to mitochondria-related metabolic pathways and the tumor immune microenvironment. These results highlight BAX as a potential prognostic biomarker for prostate cancer treated with ADT; however, further validation in larger cohorts and functional studies is warranted.<\/jats:p>","DOI":"10.3390\/genes17070804","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Genomic and Transcriptomic Analysis Identifies BAX as a Prognostic Marker of Disease Progression in Prostate Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"You-Cheng","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Pharmacy, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Fen","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, 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":[[2026,7,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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