Specific variations in cfDNA methylation level of CDH1 and Gjb1 in a mouse model with breast cancer before and after metastasis.

Breast cancer (BC) metastasis is a serious concern in BC treatment. Early diagnosis and prompt intervention are extremely important for patients. Alterations in epigenetic modifications of circulating free DNA (cfDNA) have been reported during BC occurrence, but not before or after metastasis. Therefore, this study aimed to establish a highly metastatic 4T1 BC mouse model closely resembling stage IV human BC to explore changes in cfDNA methylation modifications before and after metastasis. The timing of BC metastasis was defined based on the first visible fluorescence detection in axillary lymph nodes using in small-animal imaging. The results showed that the methylation levels of CDH1 and Gjb1 in serum cfDNA changed significantly in BC before and after metastasis, displaying trends analogous to those observed in tumor tissue DNA. The methylation levels of cfDNA can be used as candidate biomarkers for the early diagnosis and monitoring of BC metastasis.