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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.
Figueroa, Jonine D; Yang, Howard; Garcia-Closas, Montserrat; Davis, Sean; Meltzer, Paul; Lissowska, Jolanta; Horne, Hisani N; Sherman, Mark E; Lee, Maxwell.
Afiliación
  • Figueroa JD; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Yang H; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Garcia-Closas M; Institute for Cancer Research, London, UK.
  • Davis S; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Meltzer P; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Lissowska J; Department of Cancer Epidemiology and Prevention, Cancer Center and M. Sklodowska-Curie Institute of Oncology, Warsaw, Poland.
  • Horne HN; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Sherman ME; National Cancer Institute, NIH, HHS, Bethesda, MD.
  • Lee M; National Cancer Institute, NIH, HHS, Bethesda, MD.
Breast Cancer Res Treat ; 150(2): 457-466, 2015 Apr.
Article en En | MEDLINE | ID: mdl-25773928
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / ARN Mensajero / Receptores de Estrógenos / Biomarcadores de Tumor / Metilación de ADN Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2015 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / ARN Mensajero / Receptores de Estrógenos / Biomarcadores de Tumor / Metilación de ADN Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Breast Cancer Res Treat Año: 2015 Tipo del documento: Article Pais de publicación: Países Bajos