title: Vimentin DNA methylation predicts survival in breast cancer.
abstract: 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.
authors.affiliation: The University of North Carolina at Chapel Hill School of Nursing, Lab 013, Carrington Hall, CB #7460, Chapel Hill, NC 27599-7460, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Ulirsch
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: George
authors.initials: G
authors.lastname: Knafl
authors.forename: Ming Jing
authors.initials: MJ
authors.lastname: Wu
authors.forename: Brett
authors.initials: B
authors.lastname: Coleman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Theresa
authors.initials: T
authors.lastname: Swift-Scanlan
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D014746:Vimentin; C508053:ERBB2 protein, human