EphA2 ligands (for example, ephrin-A1) are expressed abundantly in different tumor types such as breast carcinoma and melanoma, and normal tissues.6 Soluble ephrin-A1 is released by cleavage of matrix metalloproteinases (MMPs) and is detected in the sera of patients with hepatocellular carcinoma.7, 8 Therefore, critical questions are how and when ligand-independent EphA2 signaling is activated in tumors. This evidence concerns the gene EFNA1 and hepatocellular carcinoma.