Chapter 1 - Cell origin, biology, and pathophysiology of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a heterogeneous disease, ranking third for the cancer-related mortalities worldwide. Hepatocytes and progenitor cells are the cells of origin and play a major role in transforming into mature HCC cells. A better knowledge of the cell origin is essential as it aids in identifying tumor growth-associated molecular mechanisms and therapeutic options. Recent advances such as genome profiling and next-generation sequencing have uncovered various genomic alterations in HCC and profiled aberrantly behaving genes in HCC. The aberrantly behaving genes in HCC are TP53, CCND1, AXIN1, TERT promoter, CTNNB1, ARID1A, and CDKN2A. The tumor heterogeneity promotes tumor progression, metastasis, disease recurrence, and chemoresistance and limits patient prognosis. Thus a better understanding of the characterization of heterogeneity in HCC is significant for clinical practice and better survival of the patient. In addition, the biomarkers profiling for HCC is very limited and is essential for clinical decision-making. This chapter provides an overview about the cell of origin and biology of HCC, cellular heterogeneity, and associated pathways that contribute to HCC progression.