CAV1 as a Potential Regulator of Endothelial-Macrophage Communication Through the CD74/MIF Pathway in Breast Cancer

Breast cancer (BRCA) is one of the most common malignancies and a leading cause of cancer-related mortality in women. We integrated predicted compound targets of Fufang Banmao Capsules with BRCA-associated genes and prioritized candidates using LASSO regression, correlation analysis, and ROC analysis. Single-cell RNA sequencing analysis then characterized their expression patterns, endothelial heterogeneity, and inferred endothelial-macrophage communication. The four key genes CAV1, CES1, PPARG, and RUNX1T1 showed the highest AUCell scores in endothelial cells. Cell-cell communication analysis inferred MIF signaling involving CD74-containing receptor complexes between endothelial cells and macrophages. Virtual knockout analysis identified CD74 among the genes predicted to be perturbed following CAV1, CES1, or RUNX1T1 knockout in endothelial cells. Further analysis revealed heterogeneous CAV1 expression across endothelial subpopulations, with relatively higher expression in ACKR1-positive and metabolic endothelial cells. Pseudotime analysis characterized variation in CAV1 expression along inferred trajectories, while regulon analysis identified distinct regulatory programs across endothelial subpopulations. Together, these findings prioritize candidate genes linked to the predicted targets of Fufang Banmao Capsules and generate hypotheses concerning their cellular context in BRCA.