Identification of Subtypes of HCC Using Bioinformatics and the Hepatocyte Differentiation Model

The developmental signaling is closely associated with tumor aggressiveness. Subclassification of human hepatocellular carcinoma (HCC) from the developmental aspect may help understand the cellular origins of liver cancer, and further assist clinical practice. Here, we establish an in vitro hepatocyte differentiation model to induce human embryonic stem cells (hESCs) differentiation through progressive steps from uncommitted endoderm patterning to the multipotent liver progenitors, and finally differentiate into mature hepatocytes. The gene expression patterns and dynamic changes during hepatocyte differentiation could be monitored through RNA-sequencing of cells at different developmental stages. Hierarchical clustering analysis and topological data analysis could be used to generate and distinguish different subtypes of HCCs according to the gene expression signatures.