Fig. 1.

Performance of a “wound response” gene expression signature in predicting breast cancer progression. (A) Unsupervised hierarchical clustering of 295 breast cancer samples using 442 available CSR genes. Each row represents a gene; each column represents a sample. The level of expression of each gene, in each sample, relative to the mean level of expression of that gene across all of the samples, is represented by using a red–green color scale as shown in the key; gray indicates missing data. The transcriptional response of each gene in the fibroblast serum response is shown on the right bar (red indicates increased expression, and green indicates reduced expression in response to serum). The dendrogram at the top indicates the similarities among the samples in their expression of the CSR genes. Two main groups of tumors were observed: one group with a gene expression pattern similar to that of serum-activated fibroblasts, termed “activated,” and a second group with a reciprocal expression pattern of CSR genes, termed “quiescent.” Two small subsets of the quiescent group with more heterogeneous expression patterns are indicated by yellow bars. (B and C) Kaplan–Meier survival curves for the two classes of tumors. Patients with tumor expression the activated wound-response signature had worse overall survival (OS) and DMFP compared to those with a quiescent wound-response signature. A total of 126 tumors were classified as activated, and 169 tumors were classified as quiescent. For activated vs. quiescent groups, 10-year OS are 50% vs. 84% (P = 5.6 × 10^-10) and 10-year DMFP are 51% vs. 75% (P = 8.6 × 10^-6), respectively.