Aberrant Vimentin Methylation Is Characteristic of Breast Cancer

Background: Epigenetic mechanisms including DNA methylation are key regulators of gene activity and may play key roles in carcinogenesis through cumulative activation and inactivation of oncogenes, tumor suppressor genes, and other genes. Increased vimentin gene expression has been reported in various tumor cell lines and tissues including breast cancer. In addition, methylation of the vimentin gene was described as a marker in several malignant tumors. Objective: The aim of this study is to determine the existence of a potential relationship between the methylation state of the vimentin gene and its prognostic value in breast cancer patients and its correlation with vimentin protein expression in the serum. Patients and Methods: The methylation status of the vimentin gene was examined in primary infiltrating ductaltumors and the surrounding normal tissues derived from 50 breast cancer patients enrolled for either modified radical mastectomy or conservative breast surgery using quantitative methylation-specific polymerase chain reaction (qMSP), serum vimentin levels were determined using ELISA, and the correlation between the methylation status and the clinicopathological findings was evaluated. Results: Out of 50 breast cancer patients, 18 (36%) exhibited positive methylation of vimentin gene while 32 (64%) exhibited negative vimentin genemethylation in their tumors. Subsequently clinicopathological data were correlated with the vimentin genemethylation score. A significant association was found between negative vimentin methylation, and both serum vimentin protein level (p < 0.001) and the triple negative breast cancer subtype (TNBCs) (p = 0.004). Using receiver-operating characteristic (ROC) curve analysis, a cut off value of <0.49 was set for the negative vimentin methylation score to distinguish between early and late stage breast cancer, and the ROC curve showed an area under the curve (AUC) of 0.684 (p = 0.029). Conclusion: Our study showed that the vimentin gene is frequently hypomethylated in breast cancer tissues, and that negative methylation status is always associated with high serum vimentin protein expression levels. Also we reported a significant association between negative vimentin methylation and TNBC subtype which is known to have an aggressive clinical course. Taken together, these results might have important implications for the design of novel therapeutic interventions for breast cancer patients. However, further studies with larger sample size are needed to validate these observations.