Vimentin knock out mouse neural stem cell RNA sequencing
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE136553 | GEO | 2020/04/05
REPOSITORIES: GEO
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Project description:Vimentin knock out mouse neural stem cell RNA sequencing
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Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed 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 in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ 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. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis.
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Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed 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 in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ 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. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis. reference x sample
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