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Prognostic Significance in Breast Cancer of a Gene Signature Capturing Stromal PDGF Signaling

Frings, Oliver ; Augsten, Martin ; Tobin, Nicholas P. ; Carlson, Joseph ; Paulsson, Janna ; Pena, Cristina ; Olsson, Eleonor LU ; Veerla, Srinivas LU orcid ; Bergh, Jonas and Ostman, Arne , et al. (2013) In American Journal of Pathology 182(6). p.2037-2047
Abstract
In this study, we describe a novel gene expression signature of platelet-derived growth factor (PDGF) activated fibroblasts, which is able to identify breast cancers with a PDGF-stimulated fibroblast stroma and displays an independent and strong prognostic significance. Global gene expression was compared between PDGF-stimulated human fibroblasts and cultured resting fibroblasts. The most differentially expressed genes were reduced to a gene expression signature of 113 genes. The biological significance and prognostic capacity of this signature were investigated using four independent clinical breast cancer data sets. Concomitant high expression of PDGF beta receptor and its cognate Ligands is associated with a high PDGF signature score.... (More)
In this study, we describe a novel gene expression signature of platelet-derived growth factor (PDGF) activated fibroblasts, which is able to identify breast cancers with a PDGF-stimulated fibroblast stroma and displays an independent and strong prognostic significance. Global gene expression was compared between PDGF-stimulated human fibroblasts and cultured resting fibroblasts. The most differentially expressed genes were reduced to a gene expression signature of 113 genes. The biological significance and prognostic capacity of this signature were investigated using four independent clinical breast cancer data sets. Concomitant high expression of PDGF beta receptor and its cognate Ligands is associated with a high PDGF signature score. This supports the notion that the signature detects tumors with PDGF-activated stroma. Subsequent analyses indicated significant associations between high PDGF signature score and clinical characteristics, including human epidermal growth factor receptor 2 positivity, estrogen receptor negativity, high tumor grade, and large tumor size. A high PDGF signature score is associated with shorter survival in univariate analysis. Furthermore, the high PDGF signature score acts as a significant marker of poor prognosis in multivariate survival analyses, including classic prognostic markers, Ki-67 status, a proliferation gene signature, or other recently described stroma-derived gene expression signatures. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Pathology
volume
182
issue
6
pages
2037 - 2047
publisher
American Society for Investigative Pathology
external identifiers
  • wos:000319781800011
  • scopus:84878238535
  • pmid:23583284
ISSN
1525-2191
DOI
10.1016/j.ajpath.2013.02.018
language
English
LU publication?
yes
id
1373b697-c7d5-4977-9dc7-d78e6f3bb238 (old id 3926978)
date added to LUP
2016-04-01 10:46:56
date last changed
2024-02-05 13:31:56
@article{1373b697-c7d5-4977-9dc7-d78e6f3bb238,
  abstract     = {{In this study, we describe a novel gene expression signature of platelet-derived growth factor (PDGF) activated fibroblasts, which is able to identify breast cancers with a PDGF-stimulated fibroblast stroma and displays an independent and strong prognostic significance. Global gene expression was compared between PDGF-stimulated human fibroblasts and cultured resting fibroblasts. The most differentially expressed genes were reduced to a gene expression signature of 113 genes. The biological significance and prognostic capacity of this signature were investigated using four independent clinical breast cancer data sets. Concomitant high expression of PDGF beta receptor and its cognate Ligands is associated with a high PDGF signature score. This supports the notion that the signature detects tumors with PDGF-activated stroma. Subsequent analyses indicated significant associations between high PDGF signature score and clinical characteristics, including human epidermal growth factor receptor 2 positivity, estrogen receptor negativity, high tumor grade, and large tumor size. A high PDGF signature score is associated with shorter survival in univariate analysis. Furthermore, the high PDGF signature score acts as a significant marker of poor prognosis in multivariate survival analyses, including classic prognostic markers, Ki-67 status, a proliferation gene signature, or other recently described stroma-derived gene expression signatures.}},
  author       = {{Frings, Oliver and Augsten, Martin and Tobin, Nicholas P. and Carlson, Joseph and Paulsson, Janna and Pena, Cristina and Olsson, Eleonor and Veerla, Srinivas and Bergh, Jonas and Ostman, Arne and Sonnhammer, Erik L. L.}},
  issn         = {{1525-2191}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{2037--2047}},
  publisher    = {{American Society for Investigative Pathology}},
  series       = {{American Journal of Pathology}},
  title        = {{Prognostic Significance in Breast Cancer of a Gene Signature Capturing Stromal PDGF Signaling}},
  url          = {{http://dx.doi.org/10.1016/j.ajpath.2013.02.018}},
  doi          = {{10.1016/j.ajpath.2013.02.018}},
  volume       = {{182}},
  year         = {{2013}},
}