PURPOSE: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). METHODS: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. RESULTS: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. CONCLUSION: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.
PURPOSE: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). METHODS: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. RESULTS: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. CONCLUSION: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.
Authors: Christopher P E Lange; Mihaela Campan; Toshinori Hinoue; Roderick F Schmitz; Andrea E van der Meulen-de Jong; Hilde Slingerland; Peter J M J Kok; Cornelis M van Dijk; Daniel J Weisenberger; Hui Shen; Robertus A E M Tollenaar; Peter W Laird Journal: PLoS One Date: 2012-11-28 Impact factor: 3.240