{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T08:13:20Z","timestamp":1789892000124,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54CA113001"],"award-info":[{"award-number":["U54CA113001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U01CA086402"],"award-info":[{"award-number":["U01CA086402"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30CA054174"],"award-info":[{"award-number":["P30CA054174"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Texas STARS award"},{"name":"Cancer Therapy and Research Center Foundation"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009395","name":"CancerCare Manitoba","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009395","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Carl Zeiss Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)\u2010related genes in patients' plasma cell\u2010free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Methyl\u2010binding domain capture sequencing (MBDCap\u2010seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and\/or post\u2010radical prostatectomy (RP) using univariate and multivariate prediction analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Putative DMRs in 13 of 30 ABP\u2010related genes were found between tumors of BCR (n<jats:italic>\u2009=\u2009<\/jats:italic>12) versus no evidence of disease (NED) (n<jats:italic>\u2009=\u2009<\/jats:italic>15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci\u2014<jats:italic>SRD5A2<\/jats:italic> and <jats:italic>CYP11A1<\/jats:italic>, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post\u2010RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Overall, increased DNA methylation of <jats:italic>SRD5A2<\/jats:italic> and <jats:italic>CYP11A1<\/jats:italic> related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post\u2010RP further suggests their utility as predictive markers for PCa recurrence. <jats:italic>Prostate 75:1790\u20131801, 2015<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23052","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T18:58:56Z","timestamp":1441220336000},"page":"1790-1801","source":"Crossref","is-referenced-by-count":28,"title":["DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence"],"prefix":"10.1002","volume":"75","author":[{"given":"Aaron M.","family":"Horning","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius A.","family":"Awe","sequence":"additional","affiliation":[{"name":"Manitoba Institute of Cell Biology University of Manitoba Winnipeg Manitoba Canada"},{"name":"Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"},{"name":"Systems Biology Research Centre School of Life Sciences, University of Sk\u00f6vde  Sk\u00f6vde Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiou\u2010Miin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health Science Center San Antonio 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University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tad","family":"Kroczak","sequence":"additional","affiliation":[{"name":"Manitoba Prostate Center University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Therapy and Research Center University of Texas Health Science Center San Antonio Texas"},{"name":"Greehey Children's Cancer Research Institute University of Texas Health Science Center San Antonio Texas"},{"name":"Department of Epidemiology &amp; Biostatistics University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor X.","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine University of Texas Health Science Center San Antonio Texas"},{"name":"Department of Epidemiology &amp; Biostatistics University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry L.","family":"Abboud\u2010Werner","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Leach","sequence":"additional","affiliation":[{"name":"Cancer Therapy and Research Center University of Texas Health Science Center San Antonio Texas"},{"name":"Department of Cellular and Structural Biology University of Texas Health Science Center San Antonio Texas"},{"name":"Department of Urology University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javior","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Cancer Therapy and Research Center University of Texas Health Science Center San Antonio Texas"},{"name":"Department of Urology University of Texas Health Science Center San Antonio Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Saranchuk","sequence":"additional","affiliation":[{"name":"Manitoba Prostate Center University of Manitoba Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darrel","family":"Drachenberg","sequence":"additional","affiliation":[{"name":"Manitoba Prostate Center University of Manitoba 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