DNA methylation screening of primary prostate tumors identifies SRD5A2 and CYP11A1 as candidate markers for assessing risk of biochemical recurrence. Issue 15 (1st September 2015)

• Record Type: Journal Article
• Authors: Horning, Aaron M.; Awe, Julius A.; Wang, Chiou‐Miin; Liu, Joseph; Lai, Zhao; Wang, Vickie Yao; Jadhav, Rohit R.; Louie, Anna D.; Lin, Chun‐Lin; Kroczak, Tad; Chen, Yidong; Jin, Victor X.; Abboud‐Werner, Sherry L.; Leach, Robin J.; Hernandez, Javior; Thompson, Ian M.; Saranchuk, Jeff; Drachenberg, Darrel; Chen, Chun‐Liang; Mai, Sabine; Huang, Tim Hui‐Ming
• Is Part Of: Prostate. Volume 75:Issue 15(2015)
• Page Start: 1790
• Page End: 1801
• Publication Date: 2015-09-01
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23052
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros23052-sec-0001" sec-type="section"> <title>BACKGROUND</title> <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)‐related genes in patients' plasma cell‐free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR).</p> </sec> <sec id="pros23052-sec-0002" sec-type="section"> <title>METHODS</title> <p>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.</p> </sec> <sec id="pros23052-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Putative DMRs in 13 of 30 ABP‐related genes were found between tumors of BCR (n<italic> = </italic>12) versus no evidence of disease (NED) (n<italic> = </italic>15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci—<italic>SRD5A2</italic> and <italic>CYP11A1</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‐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.</p> </sec> <sec id="pros23052-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Overall, increased DNA methylation of <italic>SRD5A2</italic> and <italic>CYP11A1</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‐RP further suggests their utility as predictive markers for PCa recurrence. <italic>Prostate 75:1790–1801, 2015</italic>. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>