Abstract
Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. However, the diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. A systematic search was performed to identify eligible articles for analysis. The pooled OR showed that SFRP1, SFRP2, SFRP4 and SFRP5 methylation was significantly higher in CRC and benign mucosal lesions than in normal colonic mucosa. When CRC was compared to benign mucosal lesions, SFRP1 and SFRP2 methylation had a significantly higher OR, but methylated SFRP4 and SFRP5 had a similar OR. Moreover, the pooled sensitivity, specificity and AUC (area under the curve) of methylated SFRP2 in feces of patients with CRC vs. healthy subjects was 0.71, 0.94 and 0.94, respectively. Therefore, methylation of SFRP1 and SFRP2 may be significantly correlated with CRC. However, in a study with small sample size, methylated SFRP4 and SFRP5 were not shown to be closely associated with CRC. Additionally, detection of SFRP2 methylation in feces presents a potential noninvasive biomarker for CRC diagnosis.
Highlights
Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported
Colorectal cancer (CRC) is a prevalent malignancy that develops from normal colon epithelium into either adenomas or serrated polyps, progresses to cancer via multiple sequences of histological development[22,38]
Methylated SFRP genes have been reported in the pathogenesis of CRC22,26, but the diagnostic role of gene methylation has not been evaluated in CRC
Summary
Methylation of secreted frizzled-related protein genes (SFRP) associated with the Wnt signaling pathway has previously been reported. The diagnostic role of SFRP methylation in colorectal cancer (CRC) remains unclear. In a study with small sample size, methylated SFRP4 and SFRP5 were not shown to be closely associated with CRC. Detection of SFRP2 methylation in feces presents a potential noninvasive biomarker for CRC diagnosis. Inactivation of SFRP genes leads to deregulated activation of Wnt signaling, which is related to CRC8. SFRP2 promoter methylation in feces can be a noninvasive biomarker for the diagnosis of CRC9,10. The association of methylated SFRP1 and SFRP2 has been investigated in patients with CRC in a meta-analysis[13,14], these methylation studies were conducted using a small sample size. We first determined whether SFRP1 and SFRP2 methylation was associated with CRC in feces and blood.
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