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

Akhilandeshwari Ravichandran1, James Monkman2, Ahmed M Mehdi3

  • 1School 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.

Abstract

Insights

Researchers profiled gene expression in Triple Negative Breast Cancer (TNBC) endothelial cells versus normal cells. This revealed distinct molecular profiles, offering new targets for anti-angiogenic therapies in TNBC treatment.

Area of Science:

  • Oncology
  • Vascular Biology
  • Genomics

Background:

  • Triple Negative Breast Cancer (TNBC) exhibits increased angiogenesis, promoting tumor growth and metastasis.
  • Current anti-angiogenic therapies for TNBC have shown limited clinical success.
  • Understanding the molecular characteristics of tumor-associated vasculature is crucial for developing targeted treatments.

Purpose of the Study:

  • To investigate the molecular differences between endothelial cells in TNBC tissues and normal adjacent tissues.
  • To identify unique gene expression profiles and signaling pathways in tumor-associated vasculature.

Main Methods:

  • Employed unbiased whole transcriptome spatial profiling.
  • Analyzed in situ gene expression in endothelial cells from TNBC patient tissues (n=4) and matched normal-adjacent regions.

Main Results:

  • Identified 2412 differentially expressed genes between tumor and normal endothelial cells (p_adj < 0.05).
  • Pathway enrichment analysis highlighted significant differences in cell-cell adhesion, cell-ECM adhesion, chromatin organization, and protein-DNA complex organization.

Conclusions:

  • Demonstrated unique molecular profiles and signaling pathways in tumor-associated vasculature in TNBC.
  • These findings provide a foundation for larger studies to identify potential therapeutic targets for TNBC prognosis and anti-angiogenic treatments.