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Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients

BACKGROUND: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. METHODS AND...

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Autores principales: Martin, Damali N., Boersma, Brenda J., Yi, Ming, Reimers, Mark, Howe, Tiffany M., Yfantis, Harry G., Tsai, Yien Che, Williams, Erica H., Lee, Dong H., Stephens, Robert M., Weissman, Allan M., Ambs, Stefan
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2638012/
https://www.ncbi.nlm.nih.gov/pubmed/19225562
http://dx.doi.org/10.1371/journal.pone.0004531
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author Martin, Damali N.
Boersma, Brenda J.
Yi, Ming
Reimers, Mark
Howe, Tiffany M.
Yfantis, Harry G.
Tsai, Yien Che
Williams, Erica H.
Lee, Dong H.
Stephens, Robert M.
Weissman, Allan M.
Ambs, Stefan
author_facet Martin, Damali N.
Boersma, Brenda J.
Yi, Ming
Reimers, Mark
Howe, Tiffany M.
Yfantis, Harry G.
Tsai, Yien Che
Williams, Erica H.
Lee, Dong H.
Stephens, Robert M.
Weissman, Allan M.
Ambs, Stefan
author_sort Martin, Damali N.
collection PubMed
description BACKGROUND: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. METHODS AND RESULTS: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors. CONCLUSIONS: The gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers. Notably, pathways related to tumor angiogenesis and chemotaxis could be functionally different in these two patient groups.
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spelling pubmed-26380122009-02-19 Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients Martin, Damali N. Boersma, Brenda J. Yi, Ming Reimers, Mark Howe, Tiffany M. Yfantis, Harry G. Tsai, Yien Che Williams, Erica H. Lee, Dong H. Stephens, Robert M. Weissman, Allan M. Ambs, Stefan PLoS One Research Article BACKGROUND: African-American breast cancer patients experience higher mortality rates than European-American patients despite having a lower incidence of the disease. We tested the hypothesis that intrinsic differences in the tumor biology may contribute to this cancer health disparity. METHODS AND RESULTS: Using laser capture microdissection, we examined genome-wide mRNA expression specific to tumor epithelium and tumor stroma in 18 African-American and 17 European-American patients. Numerous genes were differentially expressed between these two patient groups and a two-gene signature in the tumor epithelium distinguished between them. To identify the biological processes in tumors that are different by race/ethnicity, Gene Ontology and disease association analyses were performed. Several biological processes were identified which may contribute to enhanced disease aggressiveness in African-American patients, including angiogenesis and chemotaxis. African-American tumors also contained a prominent interferon signature. The role of angiogenesis in the tumor biology of African-Americans was further investigated by examining the extent of vascularization and macrophage infiltration in an expanded set of 248 breast tumors. Immunohistochemistry revealed that microvessel density and macrophage infiltration is higher in tumors of African-Americans than in tumors of European-Americans. Lastly, using an in silico approach, we explored the potential of tailored treatment options for African-American patients based on their gene expression profile. This exploratory approach generated lists of therapeutics that may have specific antagonistic activity against tumors of African-American patients, e.g., sirolimus, resveratrol, and chlorpromazine in estrogen receptor-negative tumors. CONCLUSIONS: The gene expression profiles of breast tumors indicate that differences in tumor biology may exist between African-American and European-American patients beyond the knowledge of current markers. Notably, pathways related to tumor angiogenesis and chemotaxis could be functionally different in these two patient groups. Public Library of Science 2009-02-19 /pmc/articles/PMC2638012/ /pubmed/19225562 http://dx.doi.org/10.1371/journal.pone.0004531 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Martin, Damali N.
Boersma, Brenda J.
Yi, Ming
Reimers, Mark
Howe, Tiffany M.
Yfantis, Harry G.
Tsai, Yien Che
Williams, Erica H.
Lee, Dong H.
Stephens, Robert M.
Weissman, Allan M.
Ambs, Stefan
Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title_full Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title_fullStr Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title_full_unstemmed Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title_short Differences in the Tumor Microenvironment between African-American and European-American Breast Cancer Patients
title_sort differences in the tumor microenvironment between african-american and european-american breast cancer patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2638012/
https://www.ncbi.nlm.nih.gov/pubmed/19225562
http://dx.doi.org/10.1371/journal.pone.0004531
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