Is methylation analysis ofSFRP2,TFPI2,NDRG4, andBMP3promoters suitable for colorectal cancer screening in the Korean population?

Abstract

Background/Aims Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. Methods A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy. The methylation status of the SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters was investigated blindly using bisulfate-modified stool DNA obtained from 111 participants. Methylation status was investigated by methylation-specific polymerase chain reaction. Results Methylated SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters were detected in 60.0%, 31.4%, 68.8%, and 40.0% of CRC samples and in 27.8%, 27.8%, 27.8%, and 33.3% of AA samples, respectively. The sensitivities obtained using 4 markers to detect CRC and AA were 94.3% and 72.2%, respectively. The specificity was 55.0%. Conclusions Our results demonstrate that the SFRP2 , TFPI2 , NDRG4 , and BMP3 promoter methylation analysis of stool sample DNA showed high sensitivity but low specificity for detecting CRC and AA. Because of the low specificity, 4 methylated markers might not be sufficient for CRC screening in the Korean population. Further large-scale studies are required to validate the methylation of these markers in the Asian population and to find new markers for the Asian population.

Novel biomarkers for the diagnosis and prognosis of colorectal cancer

“…, and WIF1, have been analyzed for the diagnosis of CRC. [82][83][84][85] To date, the United States Food and Drug Administration has approved only the Cologuard test (multitarget stool DNA test for CRC) for CRC screening. Compared to the gFOBT, the Cologuard test shows better sensitivity (13% vs. 52%) for detecting CRC.…”

Syndecan-2 Methylation as a New Biomarker for Early Detection of Colorectal Neoplasm

“…A recent study of stool DNA methylation in an Asian population, assessing the methylation of SFRP2 , TFPI2 , NDRG4 , and BMP3 promoters, showed high sensitivities of 94.3% and 72.2% to detect both CRC and advanced adenoma, respectively, but with a low specificity of 55.0%. 4 A new blood screening test that examines methylated SEPT9 (Epi proColon ® ; Epigenomics AG, Berlin, Germany) was approved by the FDA in 2016. However, a large multicenter prospective study showed low sensitivities of 48.2% and 11.2% for detecting CRC and advanced adenoma, respectively with 91.5% specificity.…”

A New Method for the Detection of Colorectal Cancer and the Precancerous Lesions: Occult Blood Testing Combination with Promoter Methylation in the Fecal Sample

“…In addition to the accurate detection for advanced-stage cancer, an ideal screening method should be able to effectively identify early-stage cancer and precursor lesions and thus reduce the subsequent risk of invasive disease. Previous studies have reported the diagnostic accuracy of the stool DNA methylation test for detecting precursor lesions, such as advanced adenoma and sessile serrated polyps, were lower than CRC [47,53,57,58]. The sensitivity of the stool DNA test for the detection of advanced precancerous lesions was around 42%-57% [32], approximately half of the detection sensitivity for CRC.…”