Rap1 signaling was among the top KEGG-enriched pathways in endothelial cells from lower ESCC, associated with calcium regulation, cytoskeletal remodeling, and cell survival, while upper ESCC endothelial cells showed enrichment in anti-apoptotic and intracellular signaling programs, including increased expression of ARHGEF12—a GEF known to activate Rap1A in specific vascular contexts [115]. This evidence concerns the gene RAP1A and esophageal squamous cell carcinoma.