title: Prognostic significance in breast cancer of a gene signature capturing stromal PDGF signaling.
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 PDGFβ 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.
authors.affiliation: Stockholm Bioinformatics Centre, Science for Life Laboratory, Solna, Sweden.
authors.forename: Oliver
authors.initials: O
authors.lastname: Frings
authors.forename: Martin
authors.initials: M
authors.lastname: Augsten
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tobin
authors.forename: Joseph
authors.initials: J
authors.lastname: Carlson
authors.forename: Janna
authors.initials: J
authors.lastname: Paulsson
authors.forename: Cristina
authors.initials: C
authors.lastname: Pena
authors.forename: Eleonor
authors.initials: E
authors.lastname: Olsson
authors.forename: Srinivas
authors.initials: S
authors.lastname: Veerla
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Arne
authors.initials: A
authors.lastname: Ostman
authors.forename: Erik L L
authors.initials: EL
authors.lastname: Sonnhammer
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D052138:Genes, Neoplasm; D006801:Humans; D053208:Kaplan-Meier Estimate; D008024:Ligands; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011379:Prognosis; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D008024:Ligands; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta