Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer.
BACKGROUND
DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer.


METHODS
Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis.


RESULTS
We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma.


CONCLUSIONS
Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.
Liu
Jun-Wei
JW
Department of Otolaryngology, Division of Head and Neck Cancer Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nagpal
Jatin K
JK
Jeronimo
Carmen
C
Lee
Ji Eun
JE
Henrique
Rui
R
Kim
Myoung Sook
MS
Ostrow
Kimberly L
KL
Yamashita
Keishi
K
van Criekinge
Vim
V
Wu
Guojun
G
Moon
Chu-So
CS
Trink
Barry
B
Sidransky
David
D
D000328:Adult; D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D051929:CD146 Antigen / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D011467:Prostate / Q000473:pathology / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C497902:MCAM protein, human