Intest Res.  2017 Oct;15(4):495-501. 10.5217/ir.2017.15.4.495.

Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?

• Park SK
• Baek HL
• Yu J
• Kim JY
• Yang HJ
• Jung YS
• Choi KY
• Kim H
• Kim HO
• Jeong KU
• Chun HK
• Kim K
• Park DI

• KMID: 2396399
• DOI: http://doi.org/10.5217/ir.2017.15.4.495

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.

Keyword

Colorectal neoplasms; Feces; DNA; Adenoma

MeSH Terms

Adenoma
Asian Continental Ancestry Group
Colonoscopy
Colorectal Neoplasms*
DNA
Feces
Genetic Markers
Humans
Mass Screening*
Methylation*
Polymerase Chain Reaction
Sensitivity and Specificity
United States Food and Drug Administration
DNA
Genetic Markers

Figure

• 

  Fig. 1 Results of the stool DNA methylation-specific PCR assay performed with samples obtained from patients with colorectal cancer (C) and advanced adenoma (A) and healthy controls (N). SFRP2, secreted frizzled-related protein 2; TFPI2, tissue factor pathway inhibitor 2; NDRG4, N-myc downstream-regulated gene 4; BMP3, bone morphogenetic protein 3.

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