Dimensions of hepatocellular carcinoma phenotypic diversity

Figure 2 The dimensions of hepatocellular carcinoma phenotypic diversity. In normal liver, the interplay between HNF4A and β-catenin governs the differential distribution of metabolic functions along the portal-to-central vein axis, which is known as liver zonation. The phenotypic spectrum of hepatocellular carcinomas across the increasing proliferation/differentiation ratios is orthogonal to the metabolic dimension, with opposing periportal vs perivenous tumor metabolic phenotypes. The third dimension, the tumor microenvironment, comprises specific features of tumor inflammation, fibrosis and immunity characterizing each hepatocellular carcinoma (HCC) subclass. Adapted from Désert et al[43].