The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective

Abstract

Hepatocellular carcinoma (HCC) typically develops from a background of cirrhosis resulting from chronic inflammation. This inflammation is frequently associated with chronic liver diseases (CLD). The advent of next generation sequencing has enabled extensive analyses of molecular aberrations in HCC. However, less attention has been directed to the chronically inflamed background of the liver, prior to HCC emergence and during recurrence following surgery. Hepatocytes within chronically inflamed liver tissues present highly activated inflammatory signaling pathways and accumulation of a complex mutational landscape. In this altered environment, cells may transform in a stepwise manner toward tumorigenesis. Similarly, the chronically inflamed environment which persists after resection may impact the timing of HCC recurrence. Advances in research are allowing an extensive epigenomic, transcriptomic and proteomic characterization of CLD which define the emergence of HCC or its recurrence. The amount of data generated will enable the understanding of oncogenic mechanisms in HCC from the CLD perspective and provide the possibility to identify robust biomarkers or novel therapeutic targets for the treatment of primary and recurrent HCC. Importantly, biomarkers defined by the analysis of CLD tissue may permit the early detection or prevention of HCC emergence and recurrence. In this review, we compile the current omics based evidence of the contribution of CLD tissues to the emergence and recurrence of HCC.

Annexins A2 and A5 are potential early biomarkers of hepatocarcinogenesis

“…However, a limitation of this hepatocarcinogen protocol for clinical application is that it does not aim to model the different etiologies identified for HCC development in humans, among which infection by different hepatitis viruses stands out. Despite the etiology, chronic liver damage is a common mechanism that may provide insight into molecular alterations in liver carcinogenesis 11 .…”

An immune and epigenetics-related scoring model and drug candidate prediction for hepatic carcinogenesis via dynamic network biomarker analysis and connectivity mapping

“…During the development of HCC, highly activated inflammatory signaling and complex mutations are observed in hepatocytes from chronic inflamed liver tissues, which is conducive for their transformation into cancerous cells [5] . The liver is a central immune modulator that maintains the balance of immune tolerance in the tumor microenvironment.…”