title: Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival.
abstract: Based on the hypothesis that features of the molecular program of normal wound healing might play an important role in cancer metastasis, we previously identified consistent features in the transcriptional response of normal fibroblasts to serum, and used this "wound-response signature" to reveal links between wound healing and cancer progression in a variety of common epithelial tumors. Here, in a consecutive series of 295 early breast cancer patients, we show that both overall survival and distant metastasis-free survival are markedly diminished in patients whose tumors expressed this wound-response signature compared to tumors that did not express this signature. A gene expression centroid of the wound-response signature provides a basis for prospectively assigning a prognostic score that can be scaled to suit different clinical purposes. The wound-response signature improves risk stratification independently of known clinico-pathologic risk factors and previously established prognostic signatures based on unsupervised hierarchical clustering ("molecular subtypes") or supervised predictors of metastasis ("70-gene prognosis signature").
authors.affiliation: Program in Epithelial Biology, Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
authors.forename: Dimitry S A
authors.initials: DS
authors.lastname: Nuyten
authors.forename: Julie B
authors.initials: JB
authors.lastname: Sneddon
authors.forename: Trevor
authors.initials: T
authors.lastname: Hastie
authors.forename: Robert
authors.initials: R
authors.lastname: Tibshirani
authors.forename: Therese
authors.initials: T
authors.lastname: Sørlie
authors.forename: Hongyue
authors.initials: H
authors.lastname: Dai
authors.forename: Yudong D
authors.initials: YD
authors.lastname: He
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van't Veer
authors.forename: Harry
authors.initials: H
authors.lastname: Bartelink
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Marc J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis; D014945:Wound Healing