Hypermethylated SFRP2 gene in fecal DNA is a high potential biomarker for colorectal cancer noninvasive screening

AIM: To investigate the feasibility of detecting hypermethylated secreted frizzled-related protein 2 (SFRP2) gene in fecal DNA as a non-invasive screening tool for colorectal cancer (CRC). METHODS: Fluorescence-based real-time PCR assay (MethyLight) was performed to analyze SFRP2 gene promoter methylation status in a blinded fashion in tumor tissues and in stool samples taken from 69 CRC patients preoperatively and at the 9th postoperative day,34 patients with adenoma ≥ 1 cm,26 with hyperplastic polyp,and 30 endoscopically normal subjects. Simultaneously the relationship between hypermethylation of SFRP2 gene and clinicopathological features was analyzed. RESULTS: SFRP2 gene was hypermethylated in 91.3% (63/69) CRC,79.4% (27/34) and 53.8% (14/26) adenoma and hyperplastic polyp tissues,and in 87.0% (60/69),61.8% (21/34) and 42.3% (11/26) of corresponding fecal samples,respectively. In contrast,no methylated SFRP2 gene was detected in mucosal tissues of normal controls,while two cases of matched fecal samples from normal controls were detected with hypermethylated SFRP2. A significant decrease (P < 0.001) in the rate of hypermethylated SFRP2 gene was detected in the postoperative (8.7%,6/69) fecal samples as compared with the preoperative fecal samples (87%,60/69) of CRC patients. Moreover,no significant associations were observed between SFRP2 hypermethylation and clinicopathological features including sex,age,tumor stage,site,lymph node status and histological grade,etc. CONCLUSION: Hypermethylation of SFRP2 gene in fecal DNA is a novel molecular biomarker of CRC and carries a high potential for the remote detection of CRC and premalignant lesions as noninvasive screening method.

Hypermethylation and aberrant expression of secreted fizzled-related protein genes in pancreatic cancer

AIM：To determine the methylation status and aberrant expression of some secreted frizzled-related protein（SFRP） genes in pancreatic cancer and explore their role in pancreatic carcinogenesis.METHODS：Methylation status and expression of SFRP genes were detected by methylation-specific PCR（MSPCR） and reverse-transcription PCR（RT-PCR） respectively.RESULTS：The frequencies of methylation for SFRP genes 1,2,4,5 were 70%,48.3%,60% and 76.7% in pancreatic cancer samples,and 21.7%,20%,10% and 36.7% in matched cancer adjacent normal tissue samples,respectively（χ^2 = 28.23,P 〈 0.0001 for SFRP gene 1;χ^2 = 10.71,P = 0.001 for SFRP gene 2;χ^2 = 32.97,P 〈 0.0001 for SFRP gene 4;χ^2 = 19.55,P 〈 0.0001 for SFRP gene 5）.Expression loss of SFRP genes 1,2,4 and 5 was found in 65%,40%,55% and 71.7% of 60 pancreatic cancer samples,and 25%,15%,18.3% and 31.7% of matched cancer adjacent normal tissue samples,respectively（χ^2 = 19.39,P 〈 0.0001 for SFRP gene 1;χ^2 = 9.40,P = 0.002 for SFRP gene 2;χ^2 = 17.37,P 〈 0.0001 for SFRP gene 4;χ^2 = 19.22,P 〈 0.0001 for SFRP gene 5）.SFRP gene 1 was methylated but not expressed in PC-3 and PANC-1,SFRP gene 2 was methylated but not expressed in PANC-1 and CFPAC-1,SFRP gene 4 was methylated but not expressed in PC-3,and SFRP gene 5was methylated but not expressed in CFPAC-1.CONCLUSION： Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer, which may be involved in pancreatic carcinogenesis.