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


RESULTS
In serum of HRCP patients, frequency of GSTP1, AR, and 14-3-3sigma hypermethylation was 32.2, 40.3, and 86.6%, respectively. In serum of patients with early disease frequency of GSTP1, AR, and 14-3-3sigma, hypermethylation was 21.4, 35.7, and 85.7%. In healthy controls, frequency of GSTP1, AR, and 14-3-3sigma hypermethylation was 0, 26.5, and 55.1%, respectively. There was a significant increase of frequency of TSG hypermethylation for GSTP1 and 14-3-3sigma 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.
Reibenwein
Jochen
J
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Pils
Dietmar
D
Horak
Peter
P
Tomicek
Birgit
B
Goldner
Gregor
G
Worel
Nina
N
Elandt
Katarzyna
K
Krainer
Michael
M
D048948:14-3-3 Proteins; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D005092:Exonucleases / Q000097:blood / Q000235:genetics*; D005095:Exoribonucleases; D015972:Gene Expression Regulation, Neoplastic; D051549:Glutathione S-Transferase pi / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D009367:Neoplasm Staging / Q000379:methods; D011401:Promoter Regions, Genetic / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000556:secondary*; D011944:Receptors, Androgen / Q000097:blood / Q000235:genetics*
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human