Additionally, a 2016 multicentre prospective Italian study demonstrated that angiopoietin-2 (ANGPT2), delta-like ligand 4 (DLL4), neuropilin (NRP)/tolloid (TLL)-like 2 (NETO2), endothelial cell-specific molecule-1 (ESM1), and nuclear receptor subfamily 4, group A, member 1 (NR4A1), in particular, were the liver five-gene signature associated with neoangiogenesis that reliably detected rapidly growing HCCs and predicted HCC-related mortality in cirrhotic patients of various aetiologies [130]. The gene discussed is ESM1; the disease is hepatocellular carcinoma.