Study of DACH1 Expression and its Epigenetic Regulators as Possible Breast Cancer-Related Biomarkers

Background: breast carcinogenesis involves both genetic and epigenetic changes. dna methylation, as well as micro-rna regulations, are the significant epigenetic phenomena dysregulated in breast cancer. herein, the expression of dach1 as a tumor suppressor gene and its promoter methylation status was analyzed in breast cancer tumors. also, the expression of three micro rnas (mir-217, mir-6807-3p, and mir- 552), which had been previously reported to target dach1, was assessed. methods: the sybr green-based real-time reverse transcription-pcr was used to determine dach1 and micro-rnas (mir-217, mir-6807-3p, and mir-552) expression in 120 ductal breast cancer tumors compared with standard control. also, the promoter methylation pattern of dach1 was investigated using the methylation-specific pcr technique. results: dach1 expression was significantly down-regulated in breast tumors (p< 0.05). about 33.5% of tumors showed dach1 promoter hyper-methylation. the studied micro-rnas, expression was negatively correlated with dach1 expression. the highest expressions of mirnas and higher dach1 promoter methylation were observed in advanced cancer situations. the kaplan-meier survival curves indicated that the overall survival was significantly poor in higher mirnas and lower dach1 expression in breast cancer patients (p<0.002). conclusion: dach1 down-regulation may be associated with a poor breast cancer prognosis. the dach1 down-regulation may be due to epigenetic regulations such as promoter methylation, especially in triple-negative cases. other factors, such as micro- rnas (mir-217, mir-6807-3p, and mir-552), may also have an impact. the elevated expression of mir-217, mir-6807-3p, and mir-552, maybe candidates as possible poor prognostic biomarkers in breast cancer management for further consideration.