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Promoter hypermethylation of GSTP1, AR, and 14‐3‐3σ in serum of prostate cancer patients and its clinical relevance
Author(s) -
Reibenwein Jochen,
Pils Dietmar,
Horak Peter,
Tomicek Birgit,
Goldner Gregor,
Worel Nina,
Elandt Katarzyna,
Krainer Michael
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20533
Subject(s) - gstp1 , dna methylation , prostate cancer , medicine , cancer , carcinogenesis , methylation , prostate , pca3 , oncology , cancer research , pathology , biology , gene , gene expression , genotype , biochemistry
OBJECTIVE Hypermethylation of tumor suppressor genes (TSG) is thought to play an important role in tumorigenesis of prostate cancer. The main focus of research was the detection of TSG hypermethylation in cancer tissue. Our aim was to evaluate the feasibility of detection of hypermethylated genes in serum of prostate cancer patients and its correlation with clinicopathological parameters. METHODS One hundred twenty‐five serum samples from 62 patients with hormone refractory prostate cancer (HRPC), 14 patients with early disease, and 49 healthy controls were examined. After DNA extraction and sodium‐bisulfite treatment, conventional methylation‐specific PCR (MSP) was performed for glutathione S‐transferase P1 (GSTP1), androgen receptor (AR), and 14‐3‐3σ. RESULTS In serum of HRCP patients, frequency of GSTP1, AR, and 14‐3‐3σ hypermethylation was 32.2, 40.3, and 86.6%, respectively. In serum of patients with early disease frequency of GSTP1, AR, and 14‐3‐3σ, hypermethylation was 21.4, 35.7, and 85.7%. In healthy controls, frequency of GSTP1, AR, and 14‐3‐3σ hypermethylation was 0, 26.5, and 55.1%, respectively. There was a significant increase of frequency of TSG hypermethylation for GSTP1 and 14‐3‐3σ in HRPC patients, in comparison with healthy controls. GSTP1 hypermethylation in HRPC patients was significantly correlated with differentiation of cancer and metastatic disease. CONCLUSIONS Hypermethylation of TSG can be detected in serum of prostate cancer patients. Some hypermethylated TSG can be detected in serum of healthy controls. GSTP1 was not detectable in controls and correlated significantly with Gleason score and stage of disease. Therefore, this gene may be a promising new tool in prostate cancer diagnosis. Prostate 67: 427–432, 2007. © 2006 Wiley‐Liss, Inc.