The in situ transcriptomic landscape of breast tumour-associated and normal adjacent endothelial cells

Ravichandran, A; Monkman, J; Mehdi, AM; Blick, T; Snell, C; Kulasinghe, A; Bray, LJ

Author(s): Ravichandran, A; Monkman, J; Mehdi, AM; Blick, T; Snell, C; Kulasinghe, A; Bray, LJ;
Details: Publication Year 2024-12-06,Volume 1870,Issue #2,Page 166985
Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publication Type: Research article
Abstract: BACKGROUND AND AIMS: Triple Negative Breast Cancer (TNBC) is associated with increased angiogenesis, which is known to aid tumour growth and metastasis. Anti-angiogenic therapies that have been developed to target this feature have mostly generated disappointing clinical results. Further research into targeted approaches is limited by a lack of understanding of the in situ molecular profile of tumour-associated vasculature. In this study, we aimed to understand the differences in the molecular profiles of tumour endothelial cells vs normal-adjacent endothelial cells in TNBC tissues. METHOD: We have applied unbiased whole transcriptome spatial profiling of in situ gene expressions of endothelial cells localized in full-face patient TNBC tissues (n = 4) and normal-adjacent regions of the same patient breast tissues. RESULTS: Our comparative analysis revealed that 2412 genes were differentially expressed (p(adj) < 0.05) between the tumour endothelial cells and normal-adjacent endothelial cells. Pathway enrichment showed the enrichment of gene sets related to cell-cell, cell-ECM adhesion, chromatin organization and remodeling, and protein-DNA complex subunit organization. CONCLUSION: Overall, the results revealed unique molecular profiles and signalling pathways of tumour-associated vasculature, which is a critical step towards larger cohort studies investigating potential targets for TNBC prognosis and anti-angiogenic treatments.
Keywords: Abnormal vasculature; Spatial profiling; Triple Negative Breast Cancer; Tumour endothelial cells; Whole transcriptome analyses
Department(s): Pathology
Publisher's Version: https://doi.org/10.1016/j.bbadis.2023.166985
Open Access at Publisher's Site: https://doi.org/10.1016/j.bbadis.2023.166985
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-19 06:43:12

Last Modified: 2024-01-19 06:48:25