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Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures

BACKGROUND: First-generation gene signatures that identify breast cancer patients at risk of recurrence are confined to estrogen-positive cases and are driven by genes involved in the cell cycle and proliferation. Previously we induced sets of stromal genes that are prognostic for both estrogen-posi...

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Autores principales: Mefford, Dwain, Mefford, Joel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377707/
https://www.ncbi.nlm.nih.gov/pubmed/22719844
http://dx.doi.org/10.1371/journal.pone.0037646
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author Mefford, Dwain
Mefford, Joel
author_facet Mefford, Dwain
Mefford, Joel
author_sort Mefford, Dwain
collection PubMed
description BACKGROUND: First-generation gene signatures that identify breast cancer patients at risk of recurrence are confined to estrogen-positive cases and are driven by genes involved in the cell cycle and proliferation. Previously we induced sets of stromal genes that are prognostic for both estrogen-positive and estrogen-negative samples. Creating risk-management tools that incorporate these stromal signatures, along with existing proliferation-based signatures and established clinicopathological measures such as lymph node status and tumor size, should better identify women at greatest risk for metastasis and death. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the strength and independence of the stromal and proliferation factors in estrogen-positive and estrogen-negative patients we constructed multivariate Cox proportional hazards models along with tree-based partitions of cancer cases for four breast cancer cohorts. Two sets of stromal genes, one consisting of DCN and FBLN1, and the other containing LAMA2, add substantial prognostic value to the proliferation signal and to clinical measures. For estrogen receptor-positive patients, the stromal-decorin set adds prognostic value independent of proliferation for three of the four datasets. For estrogen receptor-negative patients, the stromal-laminin set significantly adds prognostic value in two datasets, and marginally in a third. The stromal sets are most prognostic for the unselected population studies and may depend on the age distribution of the cohorts. CONCLUSION: The addition of stromal genes would measurably improve the performance of proliferation-based first-generation gene signatures, especially for older women. Incorporating indicators of the state of stromal cell types would mark a conceptual shift from epithelial-centric risk assessment to assessment based on the multiple cell types in the cancer-altered tissue.
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spelling pubmed-33777072012-06-20 Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures Mefford, Dwain Mefford, Joel PLoS One Research Article BACKGROUND: First-generation gene signatures that identify breast cancer patients at risk of recurrence are confined to estrogen-positive cases and are driven by genes involved in the cell cycle and proliferation. Previously we induced sets of stromal genes that are prognostic for both estrogen-positive and estrogen-negative samples. Creating risk-management tools that incorporate these stromal signatures, along with existing proliferation-based signatures and established clinicopathological measures such as lymph node status and tumor size, should better identify women at greatest risk for metastasis and death. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the strength and independence of the stromal and proliferation factors in estrogen-positive and estrogen-negative patients we constructed multivariate Cox proportional hazards models along with tree-based partitions of cancer cases for four breast cancer cohorts. Two sets of stromal genes, one consisting of DCN and FBLN1, and the other containing LAMA2, add substantial prognostic value to the proliferation signal and to clinical measures. For estrogen receptor-positive patients, the stromal-decorin set adds prognostic value independent of proliferation for three of the four datasets. For estrogen receptor-negative patients, the stromal-laminin set significantly adds prognostic value in two datasets, and marginally in a third. The stromal sets are most prognostic for the unselected population studies and may depend on the age distribution of the cohorts. CONCLUSION: The addition of stromal genes would measurably improve the performance of proliferation-based first-generation gene signatures, especially for older women. Incorporating indicators of the state of stromal cell types would mark a conceptual shift from epithelial-centric risk assessment to assessment based on the multiple cell types in the cancer-altered tissue. Public Library of Science 2012-06-18 /pmc/articles/PMC3377707/ /pubmed/22719844 http://dx.doi.org/10.1371/journal.pone.0037646 Text en Mefford, Mefford. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mefford, Dwain
Mefford, Joel
Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title_full Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title_fullStr Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title_full_unstemmed Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title_short Stromal Genes Add Prognostic Information to Proliferation and Histoclinical Markers: A Basis for the Next Generation of Breast Cancer Gene Signatures
title_sort stromal genes add prognostic information to proliferation and histoclinical markers: a basis for the next generation of breast cancer gene signatures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377707/
https://www.ncbi.nlm.nih.gov/pubmed/22719844
http://dx.doi.org/10.1371/journal.pone.0037646
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