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  • 1.
    Horning, Aaron M.
    et al.
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA.
    Awe, Julius Adebeyo
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg MB, Canada / Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Clin Genet, Gothenburg, Sweden.
    Wang, Chiou-Miin
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA.
    Liu, Joseph
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA.
    Lai, Zhao
    Univ Texas San Antonio, Hlth Sci Ctr, Canc Therapy & Res Ctr, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Greehey Childrens Canc Res Inst, San Antonio, TX, USA.
    Wang, Vickie Yao
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA.
    Jadhav, Rohit R.
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78229 USA..
    Louie, Anna D.
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78229 USA..
    Lin, Chun-Lin
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78229 USA..
    Kroczak, Tad
    Univ Manitoba, Manitoba Prostate Ctr, Winnipeg, MB, Canada.
    Chen, Yidong
    Univ Texas San Antonio, Hlth Sci Ctr, Canc Therapy & Res Ctr, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Greehey Childrens Canc Res Inst, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Dept Epidemiol & Biostat, San Antonio, TX, USA.
    Jin, Victor X.
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Dept Epidemiol & Biostat, San Antonio, TX, USA.
    Abboud-Werner, Sherry L.
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA..
    Leach, Robin J.
    Univ Texas San Antonio, Hlth Sci Ctr, Canc Therapy & Res Ctr, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Dept Cell & Struct Biol, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Dept Urol, San Antonio, TX, USA.
    Hernandez, Javior
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78229 USA..
    Thompson, Ian M.
    Univ Texas San Antonio, Hlth Sci Ctr, Canc Therapy & Res Ctr, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Dept Urol, San Antonio, TX, USA.
    Saranchuk, Jeff
    Univ Manitoba, Manitoba Prostate Ctr, Winnipeg, MB, Canada.
    Drachenberg, Darrel
    Univ Manitoba, Manitoba Prostate Ctr, Winnipeg, MB, Canada.
    Chen, Chun-Liang
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78229 USA..
    Mai, Sabine
    Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada.
    Huang, Tim Hui-Ming
    Univ Texas San Antonio, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX, USA / Univ Texas San Antonio, Hlth Sci Ctr, Canc Therapy & Res Ctr, San Antonio, TX, USA.
    DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence2015In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 15, 1790-1801 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. 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)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) 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-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, 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-RP. 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. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 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-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.

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