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

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Author

  • Oliver Frings
  • Martin Augsten
  • Nicholas P. Tobin
  • Joseph Carlson
  • Janna Paulsson
  • Cristina Pena
  • Eleonor Olsson
  • Srinivas Veerla
  • Jonas Bergh
  • Arne Ostman
  • Erik L. L. Sonnhammer
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Summary, in English

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.

Department/s

  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2013

Language

English

Pages

2037-2047

Publication/Series

American Journal of Pathology

Volume

182

Issue

6

Document type

Journal article

Publisher

American Society for Investigative Pathology

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1525-2191