The in situ transcriptomic landscape of breast tumour-associated and normal adjacent endothelial cells
With poor prognosis and low-survival rates, Triple Negative Breast Cancer (TNBC) has been associated with increased angiogenesis, which is known to aid tumour growth and metastasis. Anti-angiogenic therapies that were developed to address this have mostly generated disappointing clinical results. Further research into targeted approaches is limited by the lack of understanding of molecular profile of cancer-associated vasculature. Here, we have applied unbiased whole transcriptome spatial profiling of in situ gene expressions of endothelial cells localized in full-face patient TNBC tissues and adjacent normal breast tissues. Our comparative analysis showed that 2412 genes  were differentially expressed (padj<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. Overall, the results have revealed unique molecular profiles and signalling pathways of tumour vasculature which can potentially enable the detection of potential targets for TNBC prognosis and anti-angiogenic treatments and provide a greater understanding of metastasis . The results of this pilot study need validation in larger independent cohorts. Overall design: Differential gene expression of endothelial cells from tumor regions and normal-adjacent regions of full-face TNBC patient breast tissues (n=4).