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Updated: May 11, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer
R Joseph Bender1, Feilim Mac Gabhann
1Institute for Computational Medicine and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
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.
Insights
Triple negative breast cancer (TNBC) shows altered angiogenesis-related gene expression. Specific patterns of vascular endothelial growth factor (VEGF) and semaphorin dysregulation may predict prognosis and treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Triple negative breast cancer (TNBC) presents treatment challenges due to target scarcity and heterogeneity.
- Inhibiting angiogenesis is a potential strategy, but its effectiveness in breast cancer remains limited.
- Understanding angiogenesis-related gene expression heterogeneity is crucial for TNBC therapy.
Purpose of the Study:
- To quantify heterogeneity in angiogenesis-related gene expression in breast cancer.
- To investigate the prognostic and therapeutic relevance of identified gene expression patterns.
- To analyze the interplay between VEGF and semaphorin families in TNBC.
Main Methods:
- Microarray data from over 2,600 patient tumor samples were compiled and analyzed.
- Expression of VEGF and semaphorin ligands and receptors was assessed.
- Principal component analysis and clustering were used to identify gene expression patterns and group samples.
Main Results:
- TNBC exhibited significant dysregulation of VEGF- and semaphorin-related genes, often in a pro-angiogenesis direction.
- A signature of high VEGFA with low secreted semaphorins characterized 60% of TNBC and correlated with poorer survival in non-TNBC.
- A distinct TNBC pattern with high VEGFC expression was also identified.
Conclusions:
- Pro-angiogenic signatures involving VEGF and semaphorin pathways are prevalent in TNBC.
- These signatures may identify TNBC subtypes more responsive to anti-angiogenic therapies, particularly VEGF inhibitors.
- Identified gene expression patterns hold prognostic value for both TNBC and non-TNBC patients.
