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

Akhilandeshwari Ravichandran; James Monkman; Ahmed M Mehdi; Tony Blick; Cameron Snell; Arutha Kulasinghe; Laura J Bray

doi:10.1016/j.bbadis.2023.166985

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

Biochim Biophys Acta Mol Basis Dis. 2024 Feb;1870(2):166985. doi: 10.1016/j.bbadis.2023.166985. Epub 2023 Dec 6.

Authors

Akhilandeshwari Ravichandran¹, James Monkman², Ahmed M Mehdi³, Tony Blick², Cameron Snell⁴, Arutha Kulasinghe⁵, Laura J Bray⁶

Affiliations

¹ School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia; Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia. Electronic address: [email protected].
² Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD 4102, Australia.
³ Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD 4102, Australia; Queensland Cyber Infrastructure Foundation Ltd, Facility for Advanced Bioinformatics, Brisbane, QLD 4072, Australia.
⁴ Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Mater Pathology, Mater Hospital Brisbane, Mater Health Services, Brisbane, QLD 4101, Australia.
⁵ Frazer Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, QLD 4102, Australia. Electronic address: [email protected].
⁶ School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia; Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD 4059, Australia; Centre for the Personalised Analysis of Cancers, Queensland University of Technology, Translational Research Institute, QLD 4102, Australia; Australian Research Council (ARC) Training Centre for Cell and Tissue Engineering Technologies, Queensland University of Technology (QUT), Brisbane, QLD 4000, Australia. Electronic address: [email protected].

PMID: 38061601
DOI: 10.1016/j.bbadis.2023.166985

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Endothelial Cells / metabolism
Gene Expression Profiling
Humans
Signal Transduction / genetics
Transcriptome*
Triple Negative Breast Neoplasms* / pathology