Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Hepatocellular carcinoma (HCC) is a highly malignant disease with a poor prognosis and high mortality due to a low early diagnosis rate, resistance to systemic treatments and progression to late-stage liver disease. Owing to limitations in the detection of HCC and the lack of awareness of healthcare systems, fewer than 40% of HCC patients are eligible for surgery due to advanced stages of the disease at the time of diagnosis and the occurrence of multiple lesions in the cirrhotic or fibrotic liver. At present, the updated American Association for the Study of Liver Disease (AASLD) guidelines no longer recommend alpha-fetoprotein (AFP) testing as a part of diagnostic evaluation. Thus, it is imperative to establish a novel diagnostic strategy with high sensitivity and reliability to monitor risk factors to detect HCC at an early stage. In recent years, “liquid biopsy,” (including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)), has emerged as a technique for the characterization of circulating cells, providing a strong basis for the individualized treatment of patients. As a noninvasive detection method, liquid biopsy is expected to play an important role in the early diagnosis, dynamic monitoring of cancer patients and drug screening. In this review, we will focus on the clinical applications, recent studies and future prospects of liquid biopsy, particularly focusing on HCC.