Dimensions of hepatocellular carcinoma phenotypic diversity

Figure 1 Toward a unifying molecular classification of human hepatocellular carcinomas. Two major hepatocellular carcinoma (HCC) classes, non-proliferative and proliferative can be subdivided into four subclasses. Non-proliferative, well-differentiated HCCs comprise two subclasses with mutually exclusive metabolic features and regulatory signaling pathways: Periportal-type (HNF4α-driven) and Perivenous-type (β-catenin-driven). Proliferative, moderately-to-poorly differentiated HCCs comprise two subclasses: Wnt/TGF-β (regulated by interplays between Wnt and TGF-β ligands, leading to expression of extracellular matrix glycoproteins) and Stem/Progenitors (showing features of liver progenitor cells). Major clinical features, gene mutations and matches between the different HCC classifications are indicated. HCC: Hepatocellular carcinoma; TGF-β: Transforming growth factor beta; AFP: Alpha-fetoprotein; CTNNB1: Gene encoding β-catenin; TP53: Gene encoding p53; PP: Periportal; PV: Perivenous; ECM: Extracellular matrix; STEM: Stem/progenitor cells.