Heterogeneity of hepatocellular carcinoma contributes to cancer progression

•Angiogeneic heterogeneity correlated with tumor size (T stage).•Heterogeneity of the extracellular matrix protein expression.•Heterogeneity of the immune microenvironment (NK cells, NKT, T cells and Myeloid-derived suppressor cells).•Heterogeneity of HCC cells in gene expression, genetic variation, signaling pathways and cancer stem cells.•We discuss heterogeneity of HCC in four sections as above and their potential therapies for HCC.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease displaying differences in angiogenesis, extracellular matrix proteins, the immune microenvironment and tumor cell populations. Additionally, genetic variations and epigenetic changes of HCC cells could lead to aberrant signaling pathways, induce cancer stem cells and enhance tumor progression. Thus, the heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.