The Role of Liquid Biopsy in Hepatocellular Carcinoma Prognostication

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is one of the deadliest cancer. Clinical guidelines for the management of HCC endorse algorithms deriving from clinical variables whose performances to prognosticate HCC is limited. Liquid biopsy is the molecular analysis of tumor by-products released into the bloodstream. It offers minimally-invasive access to circulating analytes like DNA, RNA, exosomes and cells. This technology demonstrated promising results for various applications in cancers, including prognostication. This review aimed to provide a comprehensive overview of the contribution of liquid biopsy in HCC prognostication. The results suggested that liquid biopsy may be a polyvalent and valuable tool to prognosticate HCC. ABSTRACT: Showing a steadily increasing cancer-related mortality, the epidemiological evolution of hepatocellular carcinoma (HCC) is concerning. Numerous strategies have attempted to prognosticate HCC but their performance is modest; this is partially due to the heterogeneous biology of this cancer. Current clinical guidelines endorse classifications and scores that use clinical variables, such as the Barcelona Clinic Liver Cancer (BCLC) classification. These algorithms are unlikely to fully recapitulate the genomic complexity of HCC. Integrating molecular readouts on a patient-basis, following a precision-medicine perspective, might be an option to refine prognostic systems. The limited access to HCC tissue samples is an important limitation to these approaches but it could be partially circumvented by using liquid biopsy. This concept consists of the molecular analysis of products derived from a solid tumor and released into biological fluids, mostly into the bloodstream. It offers an easy and minimally-invasive access to DNA, RNA, extracellular vesicles and cells that can be analyzed with next-generation sequencing (NGS) technologies. This review aims to investigate the potential contributions of liquid biopsy in HCC prognostication. The results identified prognostic values for each of the components of liquid biopsy, suggesting that this technology may help refine HCC prognostication.