Promoter hypermethylation of GSTP1, AR, and 14-3-3σ in serum of prostate cancer patients and its clinical relevance

OBJECTIVE. Hypermethylation of tumor suppressor genes (TSG) is thought to play an importantroleintumorigenesisofprostatecancer.Themainfocusofresearchwasthedetection ofTSGhypermethylationincancertissue.Ouraimwastoevaluatethefeasibilityofdetectionof 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 methylationspecificPCR(MSP)wasperformedforglutathioneS-transferaseP1(GSTP1),androgenreceptor (AR), and 14-3-3s. RESULTS. In serum of HRCP patients, frequency of GSTP1, AR, and 14-3-3s hypermethylation was 32.2, 40.3, and 86.6%, respectively. In serum of patients with early disease frequency of GSTP1, AR, and 14-3-3s, hypermethylation was 21.4, 35.7, and 85.7%. In healthy controls, frequency of GSTP1, AR, and 14-3-3s hypermethylation was 0, 26.5, and 55.1%, respectively. There was a significant increase of frequency of TSG hypermethylation for GSTP1 and 14-3-3s 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 # 2006 Wiley-Liss, Inc.