Vimentin DNA methylation predicts survival in breast cancer
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The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition and is known to be overexpressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation using MALDI-TOF mass spectrometry in breast tumors and matched normal pairs in association with gene expression and survival in a hospital-based study of breast cancer patients. Gene expression data via qRT-PCR in cell lines and oligomicroarray data from breast tissues were correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation compared with matched normal pairs was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B, and HER2-enriched breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status, or metastatic disease and holds promise as a new prognostic biomarker for breast cancer patients.
KeywordsDNA methylation Breast cancer Vimentin Epigenetic Survival
Epidermal growth factor receptor
Recurrence free survival
University of North Carolina
The authors thank Dr. Tim Wiltshire and the Lineberger Cancer Center for permitting the use of the Mass Array Platform to carry out the methylation studies; Dr. Lisa Carey and Amy Drobish for clinical updates and medical records abstraction; and Dr. Scott Bultman for his thoughtful review of the paper. The authors gratefully acknowledge the support of the NIH/NCI Breast SPORE CA058823 to C.M. Perou, and the KL2RR025746 from the National Center for Research Resources and the Susan G. Komen Foundation KG090180 to T. Swift-Scanlan.
Conflicts of interest
The experiments described in this study comply with the current laws of the country in which they were performed. CMP is a major stockholder of Bioclassifier LLC and co-founder and managing partner of University Genomics. The other authors declare no competing interest.
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