Two distinct stem cell‐like subtypes of hepatocellular carcinoma with clinical significance and their therapeutic potentials

By analyzing gene expression data from human fetal liver cells [ 3], we identified 609-, 2538-, and 1139-gene signatures for gestational 10-week fetal liver cells, 17-week fetal liver cells, and mature hepatocytes, respectively (Supplementary Fig. Because 10- and 17-week fetal liver cells reflect different degrees of stemness of hepatic lineage, as reflected by α-fetoprotein expression (Supplementary Fig. The HS1 subtype showed higher rates of TP53 and RB1 mutations, while the HS2 subtype showed frequent IL6ST and CDKN2A mutations (Supplementary Fig. Since the HS1 subtype showed the highest microRNA expression (Supplementary Fig. In particular, YAP1 was highly activated in the HS1 subtype. Since YAP1 regulates HS and is associated with poor prognosis in HCC [ 7], we next examined the potential interaction of other transcription regulators with YAP1 by integrating the downstream target genes of each of the transcription regulators. S13B, C), suggesting that JQ1 can inhibit the growth and invasion of HCC cells by suppressing YAP1. Since JQ1 could inhibit most BET family members, we silenced the expression of BET members to identify the key members regulating YAP1.