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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

  • Epidemiology
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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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    Authors and Affiliations

    1. National Cancer Institute, NIH, HHS, Bethesda, MD, USA

      Jonine D. Figueroa, Howard Yang, Sean Davis, Paul Meltzer, Hisani N. Horne, Mark E. Sherman & Maxwell Lee

    2. Institute for Cancer Research, London, UK

      Montserrat Garcia-Closas

    3. Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland

      Jolanta Lissowska

    4. Division of Cancer Epidemiology and Genetics, Hormonal and Reproductive Epidemiology Branch, 9609 Medical Center Dr RM 7E122 MSC 9774, Bethesda, MD, 20892-9774, USA

      Jonine D. Figueroa

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    1. Jonine D. Figueroa
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    Jonine D. Figueroa and Howard Yang have equally contributed to this work.

    Mark E. Sherman and Maxwell Lee are Co-senior authors.

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    Figueroa, J.D., Yang, H., Garcia-Closas, M. et al. 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. Breast Cancer Res Treat 150, 457–466 (2015). https://doi.org/10.1007/s10549-015-3314-6

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