Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

Abstract

Background: The development of colorectal carcinoma (CRC) involves many genetic and epigenetic alterations and<br />methylation being an important epigenetic event has been described as a diagnostic and prognostic biomarker. Secreted<br />Frizzled- Related Protein 1 (SFRP1) gene regulates diverse physiological processes via the Wnt signaling. Promoter<br />hypermethylation of SFRP1 gene is an epigenetic regulation mechanism that downregulates SFRP1 protein level in the<br />tumor, and happens to be one of the significant events in colorectal carcinogenesis. We studied the clinicopathological<br />relationship of CRC including survival outcomes with SFRP1 gene promoter methylation. Methods: We evaluated<br />promoter methylation status of SFRP1 gene by methylation-specific PCR (MS-PCR) in the tumor tissue in 54 cases<br />of stage II-III CRC patients in north India. The MS-PCR result was further validated by bisulfite sequencing. Results:<br />SFRP1 gene was methylated in 72.2% cases and un-methylated in 27.8%. We found, that SFRP1 gene methylation in<br />tumor was associated with lymph node invasion (p=0.05). The mean overall survival was 22.318 months and 45.173<br />months respectively for patients with methylated and unmethylated SFRP1 gene (p= 0.010, log rank test), (HR = 17.313,<br />95% CI: 2.021-148.290 P=0.009). Conclusion: Study indicates that promoter methylation of SFRP1 gene is associated<br />with lymph-node metastasis and poor mean overall survival and it can be a prognostic marker in CRC.