title: Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Hypermethylated SFRP2 and WIF-1 genes in fecal DNA are novel and promising molecular biomarkers that have great diagnostic potential for early CRC.
authors.affiliation: 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.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Ya-Qiong
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D055088:Early Detection of Cancer / Q000379:methods; D004724:Endoscopy; D005243:Feces; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009780:Occult Blood; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012097:Repressor Proteins; D051153:Wnt Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C485569:WIF1 protein, human
keywords: Colorectal carcinoma; Methylation; Secreted frizzled-related protein 2; Stool; Wnt inhibitory factor-1