Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 10, Pages 3738-3743Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409462102
Keywords
microarray; prognosis; wound healing; metastasis; treatment decision
Categories
Funding
- NCI NIH HHS [U01 CA085129, R01 CA077097, CA 85129, CA 77097, T32 CA009151] Funding Source: Medline
- NIAMS NIH HHS [AR 050007, K08 AR050007] Funding Source: Medline
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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).
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