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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • 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
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)2037-2047
TidskriftAmerican Journal of Pathology
Volym182
Utgivningsnummer6
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa