Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. Issue 8 (28th September 2012)

• Record Type: Journal Article
• Authors: Perry, Antoinette S.; O'Hurley, Gillian; Raheem, Omer A.; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne‐Marie; Marignol, Laure; Murphy, Therese M.; Sullivan, Linda; Barrett, Ciara; Loftus, Barbara; Thornhill, John; Hewitt, Stephen M.; Lawler, Mark; Kay, Elaine; Lynch, Thomas; Hollywood, Donal
• Is Part Of: International journal of cancer. Volume 132:Issue 8(2013:Apr. 15)
• Page Start: 1771
• Page End: 1780
• Publication Date: 2012-09-28
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27798
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes <italic>SFRPs</italic> (Secreted Frizzled‐Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (<italic>i</italic>) profile Wnt signaling related gene expression and (<italic>ii</italic>) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (<italic>r</italic> = 0.76) than to benign prostatic hyperplasia (BPH; <italic>r</italic> = 0.57, <italic>p</italic> < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC‐3 cells with 5‐Aza‐CdR reactivated 39 genes (≥ 2‐fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (<italic>SFRP1</italic>), 64.86% (48/74) (<italic>SFRP2</italic>), 0% (0/20) (<italic>SFRP4</italic>) and 60% (12/20) (<italic>SFRP5</italic>). <italic>SFRP2</italic> methylation was detected at significantly lower frequencies in high‐grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), <italic>p</italic> = 0.0096), tumor adjacent benign areas (8.82%, (7/69), <italic>p</italic> < 0.0001) and BPH (11.43% (4/35), <italic>p</italic> < 0.0001). The quantitative level of <italic>SFRP2</italic> methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that <italic>SFRP2</italic> hypermethylation is a common event in prostate cancer. <italic>SFRP2</italic> methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.</p> </abstract>