Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2015; 21(9): 2629-2637
Published online Mar 7, 2015. doi: 10.3748/wjg.v21.i9.2629
Combined detection of plasma GATA5 and SFRP2 methylation is a valid noninvasive biomarker for colorectal cancer and adenomas
Xie Zhang, Yu-Fei Song, Hong-Na Lu, Dan-Ping Wang, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Zhi-Gang Huang
Xie Zhang, Yu-Fei Song, Hong-Na Lu, Xue-Song Zhang, Shi-Liang Huang, Bei-Lei Sun, Department of Gastroenterology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo 315040, Zhejiang Province, China
Dan-Ping Wang, School of Medicine, Ningbo University, Ningbo 315211, Zhejiang Province, China
Zhi-Gang Huang, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, Zhejiang Province, China
Author contributions: Zhang X and Song YF contributed equally to this work; Zhang X and Huang ZG designed the research; Zhang X, Song YF, Lu HN, Wang DP, Zhang XS, Huang SL and Sun BL performed the research; Zhang X, Song YF and Huang ZG analyzed the data; Zhang X, Song YF and Huang ZG wrote the paper.
Supported by Social Development Foundation of Ningbo, No. 2011C50022; Natural Science Foundation of Ningbo, No. 2012A610212; and the Scientific Innovation Team Project of Ningbo, No. 2013B82010.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Zhi-Gang Huang, MD, Associate Professor, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, 158# Shangtang Road, Xiacheng District, Hangzhou 310014, Zhejiang Province, China. huangzg@foxmail.com
Telephone: +86-574-87018768 Fax: +86-574-87018768
Received: September 10, 2014
Peer-review started: September 11, 2014
First decision: October 14, 2014
Revised: October 31, 2014
Accepted: December 1, 2014
Article in press: December 1, 2014
Published online: March 7, 2015
Processing time: 180 Days and 4.3 Hours
Abstract

AIM: To investigate GATA5, SFRP2, and ITGA4 methylation in plasma DNA as noninvasive biomarkers for colorectal cancer (CRC) or adenomas.

METHODS: There were 57 CRC patients, 30 adenomas patients, and 47 control patients enrolled in this study. Methylation-specific polymerase chain reaction was used to determine the promoter methylation status of GATA5, SFRP2, and ITGA4 genes in plasma DNA, and their association with clinical outcome in CRC. The predictive ability of GATA5, SFRP2, and ITGA4 methylation, individually or in combination, to detect CRC or adenomas was further analyzed.

RESULTS: Hypermethylated GATA5 was detected in plasma in 61.4% (35/57) of CRC cases, 43.33% (13/30) of adenoma cases, and 21.28% (10/47) of control cases. The hypermethylation of SFRP2 was detected in 54.39% (31/57), 40.00% (12/30), and 27.66% (13/47) in plasma samples from CRC, adenomas, and controls, respectively. ITGA4 methylation was detected in 36.84% (21/57) of plasma samples of CRC patients and in 30.00% (9/30) of plasma samples from patients with colorectal adenomas, and the specificity of this individual biomarker was 80.85% (9/47). Moreover, GATA5 methylation in the plasma was significantly correlated with larger tumor size (P = 0.019), differentiation status (P = 0.038), TNM stage (P = 0.008), and lymph node metastasis (P = 0.008). SFRP2 and ITGA4 methylation in plasma significantly correlated with differentiation status (SFRP2, P = 0.012; ITGA4, P = 0.007), TNM stage (SFRP2, P = 0.034; ITGA4, P = 0.021), and lymph node metastasis (SFRP2, P = 0.034; ITGA4, P = 0.021). From the perspective of predictive power and cost-performance, using GATA5 and SFRP2 together as methylation markers seemed the most favorable predictor for CRC (OR = 8.06; 95%CI: 2.54-25.5; P < 0.01) and adenomas (OR = 3.35; 95%CI: 1.29-8.71; P = 0.012).

CONCLUSION: A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of CRC and adenomas.

Keywords: Colorectal cancer; GATA binding protein 5; Secreted frizzled-related protein 2; Integrin, alpha 4; Hypermethylation; Methylation-specific PCR

Core tip: Hypermethylated GATA5 was identified as a novel plasma gene in colorectal cancer (CRC) and adenomas, and it showed high potential as a biomarker in plasma-based DNA testing. Furthermore, this study suggests that a combination of GATA5 and SFRP2 methylation could be used as a promising marker for the detection, diagnosis, and prognosis of CRC and adenomas.