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Updated: May 17, 2026
Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases
Published on: May 17, 2019
Gene expression analysis in human breast cancer associated blood vessels
Dylan T Jones1, Tanguy Lechertier, Richard Mitter
1Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Abstract:
Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold) in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC) of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of potentially novel anti-angiogenic targets that are likley to be, but not exclusivley, relevant to breast cancer.
Insights
Researchers identified novel anti-angiogenic targets in breast cancer. Gene analysis revealed upregulated genes in tumor blood vessels, with siRNA depletion showing significant anti-angiogenic effects in assays.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Angiogenesis is crucial for solid tumor growth, but current anti-angiogenic therapies are not universally effective.
- Tumor blood vessel molecular profiles vary significantly across cancer types, necessitating the discovery of novel, cancer-specific targets.
Purpose of the Study:
- To identify novel anti-angiogenic targets specific to invasive ductal carcinoma (IDC) of the breast.
- To validate the anti-angiogenic potential of identified genes using functional assays.
Main Methods:
- Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels from human IDC and normal breast tissue.
- Selection of candidate genes based on cellular function, endothelial cell enrichment, and anti-VEGF sensitivity.
- Functional validation using siRNA depletion in VEGF-stimulated ex vivo mouse aortic ring assays.
Main Results:
- Identified 63 significantly upregulated genes (5-72 fold) in IDC-associated angiogenic blood vessels compared to normal breast tissue.
- Confirmed upregulation of RRM2 (32-fold), ATF1 (23-fold), and HEX-B (8-fold) in IDC blood vessels.
- Demonstrated significant anti-angiogenic effects upon siRNA-mediated depletion of RRM2, ATF1, and HEX-B in mouse aortic ring assays.
Conclusions:
- The study provides proof-of-principle for identifying novel anti-angiogenic targets using microarray analysis of tumor vasculature.
- RRM2, ATF1, and HEX-B are identified as potentially novel anti-angiogenic targets, particularly relevant for breast cancer treatment.
- This approach can uncover a cohort of new therapeutic targets for various cancer types.
