Research Progress on Molecular Subtypes and Transdifferentiation Mechanisms of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) occurred with high occurrence rates and fatal incidence, and both clinical and basic research have challenges because HCC is highly heterogeneous and resistant mechanisms exist. Recently, assisted by further advances in molecular biotechnology, the HCC cells were categorized into different molecular subtypes, and the difference of gene expression profiles for various HCC subtypes was defined. These subtypes have clear differences in gene mutation signatures and the statuses of different signalling pathways, which not only determine the clinical behaviours of the tumours, but are also closely associated with both patient prognosis and drug responses. During molecular subtype evolving to cell phenotype, transdifferentiation also plays a role in promoting hepatocytes to return to biological lineage plasticity to respond to a certain microenvironment or gene mutation, developing into a stem or progenitor cell-like characteristic, and improving the plasticity and invasion capacity of tumors. Epithelial-mesenchymal transition (EMT) is an irreplaceable part of this process, giving HCC cells greater plasticity and drug resistance, particularly in high-risk subtypes. With the detailed molecular subtyping of HCC, the researchers can now not only more accurately and precisely recognise different clinical subtypes of disease but also provide a basis for identifying subtype-specific biomarkers and subtype-specific targeted therapies to optimise treatment outcomes and tackle the complexity of tumour heterogeneity. Not only is analyzing the mechanism of transdifferentiation helping to understand how HCC may develop but also helping to understand how some subtypes of HCC will have different outcomes as a result of different mechanisms, leading to better prognosis and more effective treatment in certain highly resistant subtypes.