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

Abstract

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.