E74-like Factor 5 Promoter Methylation in Circulating Tumor DNA as a Potential Prognostic Marker in Breast Cancer Patients

Document Type : Research Articles

Authors

Department of Medical Genetics, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

Abstract

Background: Epigenetic alternations, such as DNA methylation, play a crucial role in breast tumor initiation and progression. The identification of noninvasive prognostic biomarkers has great importance in cancer management. Methylated cell-free DNA (cfDNA), circulating in the blood as a convenient tumor-associated DNA marker, can be used as a minimally invasive cancer biomarker. This study aimed to evaluate the promoter methylation status of E74-like factor 5 (ELF5) tumor suppressor gene in both tumors and plasma cell-free DNA of 80 breast cancer patients, compared with normal controls. Methods: Plasma cfDNA concentrations were measured using quantitative real-time PCR, and methylation pattern in the ELF5 gene promoter region was performed using methylation-specific polymerase chain reaction (MS-PCR) technique. Results: The data revealed a statistically significant increase in cfDNA concentrations in breast cancer patients, particularly in those with higher stages of the disease, triple-negative status, and metastasis (p<0.001). ELF5 promoter region hypermethylation was observed in 70% of breast cancer patients in both plasma cfDNA and tumor tissues. Notably, all patients with lymph node involvement and distant metastatic exhibited promoter hypermethylation in the ELF5 gene. Conclusion: Our findings suggest that ELF5 promoter methylation in circulating DNA could serve as a potential non-invasive prognostic molecular marker in breast cancer patients. However, further studies are warranted to evaluate its diagnostic value.

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