TITLE:
Aberrant Vimentin Methylation Is Characteristic of Breast Cancer
AUTHORS:
F. I. Dwedar, G. I. Khalil, S. A. Nayer, A. Farouk
KEYWORDS:
DNA Methylation, Breast Cancer, Vimentin, Epigenetic, TNBCs
JOURNAL NAME:
Advances in Breast Cancer Research,
Vol.5 No.4,
October
19,
2016
ABSTRACT: 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 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.