Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma

Document Type: Research Articles

Authors

1 Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India.

2 Department of Pathology, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India.

3 Department of Surgical Gastroenterology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India.

Abstract

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

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