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NDRG4 promoter methylation potential biomarker for colorectal cancer

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Researchers have concluded that NDRG4 promoter methylation may be a biomarker for the noninvasive detection of colorectal cancer in stool samples.

The researchers used human colorectal cancer cell lines, colorectal tissue and noncancerous colon mucosa to analyze NDRG4 promoter methylation. They used quantitative methylation-specific polymerase chain reaction to examine the utility of NDRG4 promoter methylation as a biomarker in fecal DNA from 75 patients with colorectal cancer and 75 healthy participants.

In two independent series of colorectal cancers, the prevalence of NDRG4 promoter methylation was 86% and 70% compared with only 4% in noncancerous colon mucosa. The researchers also found that NDRG4 mRNA and protein expression were decreased in colorectal cancer tissue compared with noncancerous colon mucosa.

Using fecal DNA from a training set collected from patients and healthy participants to analyze NDRG4 promoter methylation, the gene had a sensitivity of 61% (95% CI, 43%-79%) and a specificity of 93% (95% CI, 90%-97%). An independent test set generated a sensitivity of 53% (95% CI, 39%-67%) and a specificity of 100% (95% CI, 86%-100%).

In an accompanying editorial, Gad Rennert, PhD, chairman of community medicine and epidemiology at Carmel Medical Center and Technion in Haifa, Israel, called NDRG4 a “promising biomarker of colorectal cancer.

“When NDRG4 promoter methylation was tested in small groups of colorectal cancer patients and healthy control subjects, it was found to have a sensitivity rate, although not yet optimal, that was higher than that previously reported for genetic stool tests,” he wrote. “This sensitivity was achieved with very high specificity in both training and validation sets. Adding this marker to a panel with other promising markers previously shown to be of relevance may further improve the precision of this type of technology for colorectal cancer screening.”

Melotte V. J Natl Cancer Inst. 2009;101:916-927.