{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:19:35Z","timestamp":1782299975045,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epigenetic changes have been reported to promote the development and progression of prostate cancer (PCa). Compared to normal prostate tissue, tumor samples from patients treated with androgen-deprivation therapy (ADT) show the hypermethylation of genes primarily implicated in PCa progression. A series of 90 radical prostatectomies was retrospectively analyzed. A total of 46 patients had undergone surgery alone (non-treated) and 44 had received ADT prior to surgery (treated). Promoter methylation analysis of the candidate genes possibly involved in PCa response to ADT (AR, ESR1, ESR2, APC, BCL2, CD44, CDH1, RASSF1, ZEB1) was conducted by pyrosequencing. The mRNA expression of differentially methylated genes was investigated by quantitative real-time PCR. Intratumoral microvessel density and ERG expression were also assessed using immunohistochemistry. A statistically significant difference in CD44 promoter methylation levels was found, with higher levels in the non-treated cases, which accordingly showed lower CD44 gene expression than the treated cases. Moreover, lower ESR1 methylation levels were associated with higher ERG expression, and the CD44 methylation levels were increased in ERG-overexpressing tumors, particularly in the treated cases. Our data suggest an interplay between ERG expression and the epigenetic modifications in key genes of prostate tumorigenesis, and that CD44 promoter methylation could serve as a promising molecular biomarker of PCa progression under androgen-deprived conditions.<\/jats:p>","DOI":"10.3390\/ijms26062516","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:39:03Z","timestamp":1741711143000},"page":"2516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CD44 Methylation Levels in Androgen-Deprived Prostate Cancer: A Putative Epigenetic Modulator of Tumor Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3393-7185","authenticated-orcid":false,"given":"Virginia","family":"Valentini","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5317-7533","authenticated-orcid":false,"given":"Raffaella","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Section of Anatomic Pathology, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-9379","authenticated-orcid":false,"given":"Valentina","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0117-1608","authenticated-orcid":false,"given":"Calogero","family":"Saieva","sequence":"additional","affiliation":[{"name":"Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research and Clinical Network (ISPRO), 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-8237","authenticated-orcid":false,"given":"Giandomenico","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Amorosi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, \u201cMagna Graecia\u201d University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Comp\u00e9rat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8030-0449","authenticated-orcid":false,"given":"Laura","family":"Ottini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-944X","authenticated-orcid":false,"given":"Gabriella","family":"Nesi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Section of Anatomic Pathology, University of Florence, 50139 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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