Digital spatial profiling identifies features of primary and locoregional metastatic vasculature in triple negative breast cancer.

Abstract

Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. Coupled with this, TNBC shows a high rate of metastasis which is known to be aided by tumour vasculature. Endothelial cells that form the lining of the tumour vasculature exhibit distinct genotype and phenotype differences compared with normal tissue vasculature. However, little is known about endothelial signatures that drive metastasis from a primary tumour, particularly in the context of immune infiltration. In this study, we utilized GeoMX Digital Spatial Profiling to investigate spatial proteomics differences in endothelial cells between primary and secondary sites of TNBC. By segmenting tissues using epithelial (PanCK), immune (CD45), and endothelial (CD31) markers, we analysed the microvasculature for a panel of 79 target proteins. In paired primary and secondary TNBC tissues, we identified significant downregulation of fibronectin (- log2(Fold-Change) = - 1.7, p < 0.001) in secondary sites. Specifically in epithelial regions, S100B was found to be downregulated in secondary microvasculature when compared to primary tumours. Additionally, metastasis-free primary tissues exhibited upregulated expression of S100B when compared to primary tissues that metastasized. Our study highlights the potential contributions of microvasculature to metastatic progression in TNBC, presenting new opportunities to explore them as potential biomarkers of TNBC metastasis.