Researchers identified NDRG4 to be a tumor suppressor gene in colorectal cancer. Additionally, they found that NDRG4 promoter methylation can be used as a biomarker for the detection of colorectal cancer from stool samples.
The study is published online June 17 in the Journal of the National Cancer Institute and is called “N-Myc Downstream-Regulated Gene 4 (NDRG4): A Candidate Tumor Suppressor Gene and Potential Biomarker for Colorectal Cancer.”
To evaluate NDRG4’s role in colorectal cancer, the researchers analyzed NDRG4 promoter methylation and expression in human colorectal cancer cell lines, noncancerous colon mucosa, and colorectal cancer tissue using methylation-specific PCR and bisulfite sequencing. NDRG4 mRNA and protein expression were studied using real-time PCR and immunohistochemistry, respectively. Tumor suppressor functions of NDRG4 were examined by colony formation, cell proliferation, as well as migration and invasion assays in colorectal cancer cell lines that were stably transfected with an NDRG4 expression construct.
They found that the prevalence of NDRG4 promoter methylation in two independent series of colorectal cancers was 86% and 70% compared with 4% in noncancerous colon mucosa. NDRG4 mRNA and protein expression were decreased in colorectal cancer tissue compared with noncancerous colon mucosa. NDRG4 overexpression in colorectal cancer cell lines suppressed colony formation, cell proliferation, and invasion.
Next, quantitative methylation-specific PCR was used to examine the utility of NDRG4 promoter methylation as a biomarker in fecal DNA from 75 colorectal cancer patients and 75 control subjects. The scientists found a sensitivity of 53% and a specificity of 100%.