Triple negative breast cancers (TNBC) are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in
breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in
breast cancer, we focused on two families--
VEGFs and
semaphorins--that compete for
neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient
tumor samples and analyzed the expression of
VEGF- and
semaphorin-related
ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of
VEGF- and
semaphorin-related genes; in particular, it appeared that expression of both
VEGF and
semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted
semaphorins was associated with 60% of triple-negative
breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify
cancers that are more susceptible to
VEGF inhibition.