CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer.
OBJECTIVE
We have noted that hypermethylation at GSTP1 in the preoperative serum of men with localized prostate cancer predicts early prostate specific antigen failure following surgical treatment. In this study we investigated the hypermethylation profile of several genes in the serum of men with localized and hormone refractory prostate cancer.


METHODS
We assayed the serum of 192 men with clinically localized prostate cancer and 18 with hormone refractory metastatic disease. A total of 35 serum samples from patients with negative prostate biopsy served as a negative control. CpG Island hypermethylation status of certain genes was assessed, including MDR1, EDNRB, CD44, NEP, PTGS2, RASSF1A, RAR-beta and ESR1. The results of hypermethylation at GSTP1 were included from a previous study.


RESULTS
CpG island hypermethylation at MDR1 was positive in 38.2% of cases without PSA recurrence and in 16.1% of those with biochemical recurrence after radical prostatectomy. DNA hypermethylation at the remaining 7 gene loci was not detected in the serum of patients with localized prostate cancer. In serum from metastatic prostate cancer cases CpG island hypermethylation was detected at MDR1 in 15 (83.3%), EDNRB in 9 (50%), RAR-beta in 7 (38.9%), GTSP1 in 5 (27.8%) and NEP or RASSF1A in 3 (16.7%). CpG island hypermethylation at CD44, PTGS2 or ESR was not detected in any samples. All histologically normal cases were negative for CpG island hypermethylation.


CONCLUSIONS
DNA hypermethylation at MDR1 was detected in cases of localized prostate cancer. CpG island hypermethylation at several gene loci was detected in men with advanced disease. No single gene was consistently observed to be hypermethylated in men with hormone refractory disease. These results suggest that the CpG island hypermethylation status of a defined panel of genes may be a useful biomarker in men with hormone refractory prostate cancer.
Bastian
Patrick J
PJ
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Palapattu
Ganesh S
GS
Yegnasubramanian
Srinivasan
S
Rogers
Craig G
CG
Lin
Xiaohui
X
Mangold
Leslie A
LA
Trock
Bruce
B
Eisenberger
Mario A
MA
Partin
Alan W
AW
Nelson
William G
WG
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000628:therapy
D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen