TGFB1 and colorectal carcinoma: In addition, CMS4 tumors have activated Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor beta (TGF-β), and Chemokine (CXC motif) Ligand 12 (CXCL12) signaling pathways, all of which cause, among the four CMS categories, higher risk of relapse and worst prognosis of CMS4 CRC after surgery [16].