Your browser doesn't support javascript.
loading
Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival.
Byun, Jung S; Singhal, Sandeep K; Park, Samson; Yi, Dae Ik; Yan, Tingfen; Caban, Ambar; Jones, Alana; Mukhopadhyay, Partha; Gil, Sara M; Hewitt, Stephen M; Newman, Lisa; Davis, Melissa B; Jenkins, Brittany D; Sepulveda, Jorge L; De Siervi, Adriana; Nápoles, Anna María; Vohra, Nasreen A; Gardner, Kevin.
Afiliação
  • Byun JS; National Institutes of Minority Health and Health Disparities, NIH, Bethesda, Maryland.
  • Singhal SK; Columbia University Medical Center, Columbia University, New York, New York.
  • Park S; National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Yi DI; National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Yan T; National Institutes of Minority Health and Health Disparities, NIH, Bethesda, Maryland.
  • Caban A; Columbia University Medical Center, Columbia University, New York, New York.
  • Jones A; National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Mukhopadhyay P; Columbia University Medical Center, Columbia University, New York, New York.
  • Gil SM; National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Hewitt SM; National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Newman L; Henry Ford Health System, Detroit, Michigan.
  • Davis MB; Henry Ford Health System, Detroit, Michigan.
  • Jenkins BD; Henry Ford Health System, Detroit, Michigan.
  • Sepulveda JL; Columbia University Medical Center, Columbia University, New York, New York.
  • De Siervi A; Laboratorio de Oncologia Molecular y Nuevos Blancos Terapeuticos, Instituto de Biologia y Medicina Experimental (IBYME), CONICET, Argentina.
  • Nápoles AM; National Institutes of Minority Health and Health Disparities, NIH, Bethesda, Maryland.
  • Vohra NA; Brody School of Medicine, East Carolina University, Greenville, North Carolina.
  • Gardner K; Columbia University Medical Center, Columbia University, New York, New York. klg2160@cumc.columbia.edu.
Clin Cancer Res ; 26(8): 1905-1914, 2020 04 15.
Article em En | MEDLINE | ID: mdl-31911546
PURPOSE: Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation. EXPERIMENTAL DESIGN: Data and biospecimens from 262 AA and 293 EA patients diagnosed with breast cancer from 2001 to 2010 at a major medical center were analyzed by IHC for functional biomarkers of luminal differentiation, including estrogen receptor (ESR1) and its pioneer factors, FOXA1 and GATA3. Integrated comparison of protein levels with network-level gene expression analysis uncovered predictive correlations with race and survival. RESULTS: Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race: ESR1 [EA HR = 0.47; 95% confidence interval (CI), 0.31-0.72 and AA HR = 0.77; 95% CI, 0.48-1.18]; FOXA1 (EA HR = 0.38; 95% CI, 0.23-0.63 and AA HR = 0.53; 95% CI, 0.31-0.88), and GATA3 (EA HR = 0.36; 95% CI, 0.23-0.56; AA HR = 0.57; CI, 0.56-1.4). In addition, we identify genes in the downstream regulons of these biomarkers highly correlated with race and survival. CONCLUSIONS: Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical outcome. Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Regulação Neoplásica da Expressão Gênica / População Negra / População Branca / Receptor alfa de Estrogênio / Fator de Transcrição GATA3 / Fator 3-alfa Nuclear de Hepatócito Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged País/Região como assunto: America do norte Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Regulação Neoplásica da Expressão Gênica / População Negra / População Branca / Receptor alfa de Estrogênio / Fator de Transcrição GATA3 / Fator 3-alfa Nuclear de Hepatócito Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged País/Região como assunto: America do norte Idioma: En Ano de publicação: 2020 Tipo de documento: Article