For example, besides e-cadherin (CDH1), FAH, PNPLA3, GSTT1, ATP7B, SERPINA1, NFE2L2, CUL3 and MDM2 (all downregulated both in poorly differentiated cell lines and tumours), the other ‘HCC-associated’ genes such as FRK, HNF1A, ARID1B, KEAP1, β-catenin (CTNNB1), FGF19, LGR5 and glutamine synthetase (GLUL) were lowly expressed in poorly differentiated cell lines (i.e. more expressed in well-differentiated cells) and consistently upregulated in human liver tumours (Fig. 1d). Here, CUL3 is linked to hepatocellular carcinoma.