Observational Study
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World J Gastroenterol. May 28, 2014; 20(20): 6329-6335
Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.6329
Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer
Hu Zhang, You-Qing Zhu, Ya-Qiong Wu, Ping Zhang, Jian Qi
Hu Zhang, You-Qing Zhu, Jian Qi, Department of Gastroenterology and Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Hu Zhang, Ping Zhang, Department of Gastroenterology, Hubei Provincial Corps Hospital, Chinese People’s Armed Police Force, Wuhan 430061, Hubei Province, China
Ya-Qiong Wu, Department of Dermatology, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China
Author contributions: Zhu YQ and Qi J designed this study and critically revised the article; Zhang H, Wu YQ and Zhang P were responsible for data analysis and interpretation of the results; Zhang H drafted the manuscript; all authors read and approved the final manuscript to be published.
Supported by The National Natural Science Foundation of China, No. 81101868; The Natural Science Foundation of Hubei Province of China, No. 2011CDB505
Correspondence to: Jian Qi, PhD, MD, Department of Gastroenterology and Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan 430071, Hubei Province, China. qiqidelizl@aliyun.com
Telephone: +86-27-87336141 Fax: +86-27-87336141
Received: November 7, 2013
Revised: February 20, 2014
Accepted: March 19, 2014
Published online: May 28, 2014
Abstract

AIM: To investigate the feasibility of detecting aberrantly hypermethylated Wnt-antagonist gene promoters (SFRP2 and WIF-1) in fecal DNA as non-invasive biomarkers for early colorectal cancer (CRC).

METHODS: The methylation-specific polymerase chain reaction assay was performed to blindly analyze the methylation status of SFRP2 and WIF-1 gene promoters in fecal samples from 48 subjects with CRC, 35 with adenomas, 32 with hyperplastic polyps and 30 endoscopically normal subjects. Additionally, we compared the diagnostic efficiency of measuring the hypermethylated SFRP2 and WIF-1 genes in the feces to the fecal occult blood test (FOBT) for the early detection of CRC.

RESULTS: Hypermethylated SFRP2 was detected in the feces of 56.3% (27/48) of CRC cases, 51.4% (18/35) of adenoma cases and 12.5% (4/32) of patients with hyperplastic polyps. The hypermethylation of WIF-1 was detected in 60.4% (29/48), 45.7% (16/35) and 18.7% (6/32) of fecal samples from CRC, adenoma and hyperplastic polyp patients, respectively. At least one hypermethylated gene was detected in 81.3% (39/48) of CRC and 65.7% (23/35) of adenoma samples. In contrast, only a hypermethylated WIF-1 gene was detected in one case of normal fecal samples. Moreover, no significant associations were observed between SFPR2 and WIF-1 hypermethylation and clinicopathological features. Additionally, 81.8% of CRC cases diagnosed as Dukes A stage or advanced adenomas had at least one hypermethylated gene detected, while the detection rate with the FOBT was only 31.8% (P < 0.001).

CONCLUSION: Hypermethylated SFRP2 and WIF-1 genes in fecal DNA are novel and promising molecular biomarkers that have great diagnostic potential for early CRC.

Keywords: Colorectal carcinoma, Secreted frizzled-related protein 2, Wnt inhibitory factor-1, Stool, Methylation

Core tip: Currently available approaches for the early detection of colorectal carcinoma (CRC) are suboptimal. The analysis of methylation markers in the stool as a non-invasive test is important for the early diagnosis of CRC. The epigenetic silencing of Wnt antagonist genes occurs in the early stages of CRC, and up to 90% of colorectal cancers result in the aberrant activation of Wnt signaling. In our study, we found that hypermethylated SFRP2 and WIF-1 genes in fecal DNA are novel and promising molecular biomarkers that have a great potential for the diagnosis of early CRC.