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. Author manuscript; available in PMC: 2014 Aug 29.
Published in final edited form as: Cell. 2013 Aug 29;154(5):1060–1073. doi: 10.1016/j.cell.2013.07.036

Figure 2. CAF Content in TN Tumors is Linked to Bone Metastasis.

Figure 2

(A) Box-whisker plots showing the expression of various cancer-associated stromal signatures (Allinen et al., 2004) in TN tumors of the EMC-MSK dataset, according to SRS status. The expression level of each signature in each tumor is represented by the average probe intensity of the genes comprising the signature. Difference between SRS+ and SRS- tumors were tested using Wilcoxon signed rank test. ***: p < 0.0001. “n.s.”: no statistical difference.

(B) Venn diagram showing the overlap between the SRS-associated genes and the CAF signature genes, and identities of the six overlapping genes. p value was calculated by Fisher’s exact test.

(C) Unsupervised hierarchical clustering of TN tumors from the EMC-MSK dataset by CAF signature. SRS+ status is indicated by red sticks above the heatmap. Small arrows point to CXCL12 and IGF1 gene probes. Red and green bars left to the heatmap indicate genes that are over- or under- expressed in CAF signature, respectively.

(D) Gene Set Enrichment Analysis revealed a strong association between SRS status and the enrichment of CAF signature genes.

(E) Representative examples and scores of alpha smooth muscle actin (αSMA) immunohistochemical staining of TN breast tumor samples. Scale bar, 200µm.

(F) Box-whisker plots showing the mean CAF signature score (see Methods) in tumor tissues microarrays with matched microarray data. The definition and sample size of each category are indicated. Statistical significance is assessed using one-way ANOVA.

(G) Box-whisker plots showing the expression of CAF signature in 65 breast cancer metastasis samples from different sites. The number of metastases at each site is indicated in parentheses. The expression in bone metastases was significantly higher (* p < 0.0001, Wilcoxon test) compared to all other sites combined.

(H–I) Kaplan-Meier plots of cumulative bone (H) and lung (I) metastasis-free survival in TN patients according to CAF signature. The median CAF signature score is used as a cutoff to separate CAF+ and CAF- cases. Cases without clinical follow-up information are omitted. The cases included in this analysis are TN samples with matched TMA and microarray data. Numbers of relapse cases over total cases in each category are indicated in brackets. P value was calculated according to log rank test.

See also Figure S2.