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Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

Abstract
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.
AuthorsR Joseph Bender, Feilim Mac Gabhann
JournalPloS one (PLoS One) Vol. 8 Issue 5 Pg. e61788 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23667446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Semaphorins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
Topics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic (genetics)
  • Humans
  • Microarray Analysis
  • Neovascularization, Pathologic (genetics)
  • Principal Component Analysis
  • Semaphorins (genetics, metabolism)
  • Triple Negative Breast Neoplasms (classification, genetics, metabolism)
  • Vascular Endothelial Growth Factor A (metabolism)

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