Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer.

Abstract

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.

• Authors: Jun-Wei Liu, Jatin K Nagpal, Carmen Jeronimo, Ji Eun Lee, Rui Henrique, Myoung Sook Kim, Kimberly L Ostrow, Keishi Yamashita, Vim van Criekinge, Guojun Wu, Chu-So Moon, Barry Trink, David Sidransky
• Journal: The Prostate (Prostate) Vol. 68 Issue 4 Pg. 418-26 (Mar 01 2008) ISSN: 0270-4137 [Print] United States
• PMID: 18196513 (Publication Type: Journal Article)
• Copyright: Copyright 2008 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• CD146 Antigen
• MCAM protein, human

Topics

• Adult
• Aged
• Base Sequence
• Biomarkers, Tumor (genetics)
• CD146 Antigen (genetics)
• Cell Line, Tumor
• DNA Methylation
• Gene Expression Regulation, Neoplastic
• Genetic Testing
• Humans
• Male
• Middle Aged
• Neoplasm Staging (methods)
• Prostate (pathology, physiology)
• Prostatic Neoplasms (genetics, pathology)