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 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.

Epigenetics of SFRP1: The Dual Roles in Human Cancers

“…A recent study by Kumar et al showed promoter methylation of SFRP1 is associated with lymph node metastasis and poor mean overall survival (OS) in CRC. The majority of CRC samples in this study are methylated at SFRP1 with 72.2% methylation frequency [99]. On the contrary, Liu and colleagues postulated that the co-hypermethylation of SFRP1 and SFRP2 were suggested as independent prognostic predictors of survival advantage in postoperative CRC patients [100], whereby silencing of SFRP1 and SFRP2 by hypermethylation lead to a better prognosis.…”

Novel SFRP2 DNA Methylation Profile Following Neoadjuvant Therapy in Colorectal Cancer Patients with Different Grades of BMI

“…According to the literature, epigenetic remodeling of several genes ( KRAS, APC, p53, DCC, genes of the Rho family of GTPases, MACC1, Met, MTA1, RASSF1A, SFRP1 , etc.) are associated with malignant cellular transformation, progression, invasion, and metastasis in colorectal cancers [5,6,7]. Consequently, aberrant DNA methylation also offers an opportunity for its exploitation as ideal biomarkers for CRC prediction, diagnosis, and prognosis [8].…”

DNA methylation of SFRP1, SFRP2, and WIF1 and prognosis of postoperative colorectal cancer patients

“…Galamb et al also proposed that hypermethylation of the SFRP1 promoter was associated with aging [35]. Kumar et al reported that SFRP1 promoter methylation was associated with lymph nodes metastasis [19]. Bartak discovered that the SFRP1 methylation was not connected with lymph node metastasis [36].…”

“…Rawson et al discovered that SFRP1 methylation was not associated with recurrence-free survival in two large populations of CRC patients [18]. However, Kumar et al found that promoter hypermethylation of SFRP1 might be related to the poor prognosis of CRC [19]. Tang et al revealed that promoter methylation of SFRP2 in CRC tissues could be used as an independent prognostic factor for overall survival [20].…”