Howard Y. Chang1, Dimitry S.A. Nuyten1, Julie B. Sneddon1, Trevor Hastie1, Robert Tibshirani1, Thérese Sørlie1, Hongyue Dai1, Yudong D. He1, Laura J. van’t Veer1, Harry Bartelink1, Matt van de Rijn1, Patrick O. Brown1,2, Marc J. van de Vijver1
1Program in Epithelial Biology, Departments of Biochemistry, Health Research and Policy, and Pathology, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Departments of Diagnostic Oncology and Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Rosetta Inpharmatics, Seattle, WA 98109; and Norwegian Radium Hospital, 0310 Oslo, Norway
2The Netherlands Cancer Institute, Plesmanlaan 121 1066 CX Amsterdam, The Netherlands
Tóm tắt
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”).
