engleski

Methylation-associated silencing of SFRP1 gene in high-grade serous ovarian carcinomas

Wnt is a highly conserved signaling pathway responsible for tissue regeneration, maintenance regulation and differentiation of stem cells in the adult organism. Its aberrant activation through reduced expression of Wnt signaling pathway inhibitors, such as proteins from the SFRP family, is typical for development of many tumors. In the present study we explored SFRP1 protein expression and gene DNA methylation status in a cohort of serous ovarian carcinomas. Ovarian serous carcinoma tissue samples including 11 low- grade (LGSOC), 42 high-grade serous ovarian carcinomas (HGSOC) and 5 normal ovarian tissues (controls) were immunohistochemically stained for SFRP1 protein expression and semi-quantitative analyzed. DNA methylation pattern of SFRP1 gene was analyzed by methylation-specific PCR (MSP) in 8 LGSOC samples, 13 HGSOC and all control samples. In all healthy ovaries unmethylated SFRP1 gene and strong SFRP1 protein expression were found indicating an excellent concordance between SFRP1 gene methylation and protein expression. SFRP1 protein expression was significantly higher in healthy ovaries compared with both LGSOC and HGSOC (p<0.05). DNA isolated from LGSOC showed almost a complete lack of SFRP1 gene methylation while DNA isolated from HGSOC showed SFRP1 gene methylation in 7/13 (54%) of tested samples. Our preliminary data indicate loss of SFRP1 protein expression caused by the SFRP1 promoter methylation in high- grade serous ovarian carcinomas.

SFRP1 ; Wnt signaling pathway ; DNA methylation ; Serous ovarian carcinoma ; Normal ovary

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