However, we noticed that the combination of pten and tp53 was often correlative with high-grade histology and poor prognosis in zebrafish (Figs. 4, 5), suggesting that TP53 mutation-induced the regulation of certain downstream targets, including VEGF-A, CDKN1A, BAX, IGFBP3, MDM2, FAS [84, 85], might be critical for the progression pathway of hepatocarcinogenesis, which is consistent with the previous report that TP53 mutations in HCC patients were usually accompanied by worse clinical stage and prognosis [86]. This evidence concerns the gene PTEN and hepatocellular carcinoma.