A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis. Issue 12 (24th June 2014)

• Record Type: Journal Article
• Authors: Ashour, Nadia; Angulo, Javier C.; Andrés, Guillermo; Alelú, Raúl; González‐Corpas, Ana; Toledo, María V.; Rodríguez‐Barbero, José M.; López, Jose I.; Sánchez‐Chapado, Manuel; Ropero, Santiago
• Is Part Of: Prostate. Volume 74:Issue 12(2014)
• Page Start: 1171
• Page End: 1182
• Publication Date: 2014-06-24
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22833
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22833-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors.</p> </sec> <sec id="pros22833-sec-0002" sec-type="section"> <title>METHODS</title> <p>Genome‐wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered.</p> </sec> <sec id="pros22833-sec-0003" sec-type="section"> <title>RESULTS</title> <p>We found 41 genes hypermethylated in more than 20% of the tumors analyzed (<italic>P</italic> < 0.01). Of these, we newly identified <italic>GSTM2</italic> and <italic>PENK</italic> as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico‐pathological indicators of poor prognosis: a high Gleason score, elevated Ki‐67, and advanced disease. Of these, we found simultaneous hypermethylation of <italic>CFTR</italic> and <italic>HTR1B</italic> to be common in patients with a high Gleason score and high Ki‐67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer‐specific mortality (log‐rank test, <italic>P</italic> = 0.007) and biochemical recurrence‐free survival (log‐rank test, <italic>P</italic> = 0.0008).</p> </sec> <sec id="pros22833-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Our findings strongly indicate that epigenetic silencing of <italic>GSTM2</italic> and <italic>PENK</italic> is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous <italic>HTR1B</italic> and <italic>CFTR</italic> hypermethylation could help discriminate aggressive from indolent prostate tumors. <italic>Prostate 74:1171–1182, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>