Detection of aberrant methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions

Abstract

AIM: To i nve s t i g a t e t h e fe a s i b i l i ty o f d e t e c t i n gmethylated fecal DNA as a screening tool for colorectal carcinoma (CRC) and precancerous lesions. METHODS:Methylated secreted frizzled-related protein gene 2 (SFRP2 ), hyperplastic polyposis protein gene (HPP1 ) and O 6 -methylguanine-DNA methyltransferase gene (MGMT ) in stools from 52 patients with CRC, 35 patients with benign colorectal diseases and 24 normal individuals were analyzed using methylation-specific PCR.RESULTS: Methylated SFRP2 , HPP1 and MGMT were detected in 94.2%, 71.2%, 48.1% of CRC patients and 52.4%, 57.1%, 28.6% of adenoma patients, respectively. The overall prevalence of fecal DNA with at least one methylated gene was 96.2% and 81.8% in patients with CRC and precancerous lesions, respectively. In contrast, only one of the 24 normal individuals revealed methylated DNA. These results indicated a 93.7% sensitivity and a 77.1% specificity of the assay for detecting CRC and precancerous lesions. CONCLUSION:Methylation testing of fecal DNA using a panel of epigenetic markers may be a simple and promising non-invasive screening method for CRC and precancerous lesions.

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease

“…Detection of CpG island methylation in human DNA isolated from stool (Belshaw et al, 2004;Leung et al, 2004;Chen et al, 2005;Zitt et al, 2007) or serum (Zou et al, 2002;Leung et al, 2005;Nakayama et al, 2007;Lofton-Day et al, 2008) has been proposed as a new strategy for the early diagnosis of colorectal neoplasia. Other studies with comparable series have reported high sensitivities for different methylation markers used alone (Chen et al, 2005;Lenhard et al, 2005;Huang et al, 2007a;Wang and Tang, 2008) or in combination (Leung et al, 2004;Petko et al, 2005;Huang et al, 2007b;Lofton-Day et al, 2008), although a wider application is usually hinder by a limited specificity.…”

Advances in epigenetic biomarker research in colorectal cancer

“…Further studies are needed to compare these panels and kits and discover their advantages and limitations. Ultimately, the tion of CRC and a small number of advanced adenomas reached a sensitivity and specificity of 96% [58] . A followup study found that SFRP2 methylation was detectable in the stool of almost half of all patients with hyperplastic polyps or colorectal adenomas [53] , further supporting its use in the detection of premalignant lesions.…”

Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer

“…Loss of SFRP2 expression due to promoter methylation has been frequently observed in many tumors, including colorectal, ovarian, breast, gastric and liver cancers [17,[20][21][22][23]. Several earlier studies have demonstrated that the frequency of SFRP2 promoter methylation in fecal DNA is markedly increased in CRC patients compared with normal healthy controls [24][25], suggesting the SFRP2 hypermethylation in fecal DNA as a potential molecular biomarker of CRC. In this study, we extended the previous work and systematically evaluated the diagnostic potentials of SFRP2 promoter methylation in tumor tissue, stool and serum DNA samples in CRC.…”