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Possible Tumor Suppressor and Biomarker in Colorectal Cancer

The expression of N-Myc downstream-regulated gene 4 (NDRG4), a possible tumor suppressor gene in colorectal cancer, is frequently inactivated by promoter methylation. Melotte et al. (p. 916 ) examined NDRG4 expression in normal human colon mucosa and human colorectal cancer tissue and in colorectal cancer cell lines that stably overexpressed NDRG4. They then tested the potential utility of NDRG4 promoter methylation as a biomarker for early detection of colorectal cancer in stool from colorectal cancer patients and subjects without colorectal cancer. NDRG4 promoter methylation was more prevalent in colorectal cancers than in noncancerous colon mucosa. NDRG4 mRNA and protein expression was decreased in colorectal cancer tissue compared with noncancerous colon mucosa. NDRG4 overexpression in human colorectal cancer cells inhibited colony formation and cell proliferation and invasion in vitro. A methylation-specific polymerase chain reaction assay for NDRG4 promoter methylation identified the presence of colorectal cancer in 53% of colorectal cancer cases and correctly categorized a subject as cancer free 100% of the time. The authors conclude that NDRG4 may be a tumor suppressor gene in colorectal cancer and that NDRG4 promoter methylation is a potential biomarker for the noninvasive detection of colorectal cancer in stool samples.