The analysis of HCC specimens as well as of nodules obtained from mice undergoing DEN/CDAA showed a positive and significant correlation between NAE1 and HIF-2α transcript levels was detected, a novel finding which is consistent with data reporting a significant increase in global NEDDylation in human HCC that, in turn, is associated with poorest prognosis [31]. The gene discussed is NAE1; the disease is hepatocellular carcinoma.