Intest Res  
Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population?
Soo-Kyung Park1,2*, Hae Lim Baek1*, Junghee Yu1, Ji Yeon Kim3, Hyo-Joon Yang1,2, Yoon Suk Jung1,2, Kyu Yong Choi1,2, Hungdai Kim2,4, Hyung Ook Kim2,4, Kyung Uk Jeong2,4, Ho-Kyung Chun2,4, Kyungeun Kim2,5, Dong Il Park1,2
1Division of Gastroenterology, Department of Internal Medicine and 2Gastrointestinal Cancer Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, 3Comprehensive Health Care Center, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Departments of 4Surgery and 5Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
*These authors contributed equally to this study.
Correspondence to: Dong Il Park, Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea. Tel: +82-2-2001-2059, Fax: +82-2-2001-2049, E-mail: diksmc.park@samsung.com
Received: December 13, 2016; Revised: March 10, 2017; Accepted: March 20, 2017; Published online: August 2, 2017.
© Korean Association for the Study of Intestinal Diseases. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 55.5%. 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.
Keywords: Colorectal neoplasms; Feces; DNA; Adenoma


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