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01-04-2015 | Epidemiology

Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression, data identifies a methylation expression index (MEI) robustly associated with survival of ER-positive breast cancer patients

Authors: Jonine D. Figueroa, Howard Yang, Montserrat Garcia-Closas, Sean Davis, Paul Meltzer, Jolanta Lissowska, Hisani N. Horne, Mark E. Sherman, Maxwell Lee

Published in: Breast Cancer Research and Treatment | Issue 2/2015

Abstract

Identification of prognostic gene expression signatures may enable improved decisions about management of breast cancer. To identify a prognostic signature for breast cancer, we performed DNA methylation profiling and identified methylation markers that were associated with expression of ER, PR, HER2, CK5/6, and EGFR proteins. Methylation markers that were correlated with corresponding mRNA expression levels were identified using 208 invasive tumors from a population-based case–control study conducted in Poland. Using this approach, we defined the methylation expression index (MEI) signature that was based on a weighted sum of mRNA levels of 57 genes. Classification of cases as low or high MEI scores was related to survival using Cox regression models. In the Polish study, women with ER-positive low MEI cancers had reduced survival at a median of 5.20 years of follow-up, HR = 2.85 95 % CI = 1.25–6.47. Low MEI was also related to decreased survival in four independent datasets totaling over 2500 ER-positive breast cancers. These results suggest that integrated analysis of tumor expression markers, DNA methylation, and mRNA data may be an important approach for identifying breast cancer prognostic signatures. Prospective assessment of MEI along with other prognostic signatures should be evaluated in future studies.

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Title: Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression, data identifies a methylation expression index (MEI) robustly associated with survival of ER-positive breast cancer patients
Authors: Jonine D. Figueroa
Howard Yang
Montserrat Garcia-Closas
Sean Davis
Paul Meltzer
Jolanta Lissowska
Hisani N. Horne
Mark E. Sherman
Maxwell Lee
Publication date: 01-04-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3314-6

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