Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

Hdl Handle:
http://hdl.handle.net/10147/324052
Title:
Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.
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
Affiliation:
Prostate Molecular Oncology, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Ireland. aperry@tcd.ie
Citation:
Perry AS et al. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. Int. J. Cancer 2013, 132 (8):1771-80
Journal:
International journal of cancer. Journal international du cancer
Issue Date:
15-Apr-2013
URI:
http://hdl.handle.net/10147/324052
DOI:
10.1002/ijc.27798
PubMed ID:
22915211
Abstract:
Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (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 (i) profile Wnt signaling related gene expression and (ii) 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 (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 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) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 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 SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
Item Type:
Article
Language:
en
Keywords:
DNA Methylation; Epigenesis, Genetic; Gene Expression Profiling; Membrane Proteins/genetics
MeSH:
Adult; Aged; Cell Line, Tumor; DNA Methylation; Epigenesis, Genetic; Gene Expression Profiling; Humans; Male; Membrane Proteins; Middle Aged; Promoter Regions, Genetic; Prostatic Neoplasms; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction
ISSN:
1097-0215

Full metadata record

DC FieldValue Language
dc.contributor.authorPerry, Antoinette Sen_GB
dc.contributor.authorO'Hurley, Gillianen_GB
dc.contributor.authorRaheem, Omer Aen_GB
dc.contributor.authorBrennan, Kevinen_GB
dc.contributor.authorWong, Simonen_GB
dc.contributor.authorO'Grady, Anthonyen_GB
dc.contributor.authorKennedy, Anne-Marieen_GB
dc.contributor.authorMarignol, Laureen_GB
dc.contributor.authorMurphy, Therese Men_GB
dc.contributor.authorSullivan, Lindaen_GB
dc.contributor.authorBarrett, Ciaraen_GB
dc.contributor.authorLoftus, Barbaraen_GB
dc.contributor.authorThornhill, Johnen_GB
dc.contributor.authorHewitt, Stephen Men_GB
dc.contributor.authorLawler, Marken_GB
dc.contributor.authorKay, Elaineen_GB
dc.contributor.authorLynch, Thomasen_GB
dc.contributor.authorHollywood, Donalen_GB
dc.date.accessioned2014-07-31T13:33:02Z-
dc.date.available2014-07-31T13:33:02Z-
dc.date.issued2013-04-15-
dc.identifier.citationPerry AS et al. Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer. Int. J. Cancer 2013, 132 (8):1771-80en_GB
dc.identifier.issn1097-0215-
dc.identifier.pmid22915211-
dc.identifier.doi10.1002/ijc.27798-
dc.identifier.urihttp://hdl.handle.net/10147/324052-
dc.description.abstractAberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (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 (i) profile Wnt signaling related gene expression and (ii) 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 (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 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) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 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 SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to International journal of cancer. Journal international du canceren_GB
dc.subjectDNA Methylationen_GB
dc.subjectEpigenesis, Geneticen_GB
dc.subjectGene Expression Profilingen_GB
dc.subjectMembrane Proteins/geneticsen_GB
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCell Line, Tumor-
dc.subject.meshDNA Methylation-
dc.subject.meshEpigenesis, Genetic-
dc.subject.meshGene Expression Profiling-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMembrane Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshProstatic Neoplasms-
dc.subject.meshReal-Time Polymerase Chain Reaction-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.titleGene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.en_GB
dc.typeArticleen
dc.contributor.departmentProstate Molecular Oncology, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Ireland. aperry@tcd.ieen_GB
dc.identifier.journalInternational journal of cancer. Journal international du canceren_GB
dc.description.fundingNo fundingen
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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