Detection of promoter hypermethylation of Wnt antagonist genes in fecal samples for diagnosis of early colorectal cancer

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 comparedthe 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-1was detected in 60.4%(29/48),45.7%(16/35)and18.7%(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-1genes in fecal DNA are novel and promising molecular biomarkers that have great diagnostic potential for early CRC.