The use of cfDNA for HCC surveillance and prognosis

ABSTRACT Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. Its incidence is rising faster than any other cancer in the United States and it remains one of the leading causes of cancer-related deaths worldwide. While advancements in massive parallel sequencing and integration of ‘omics information have transformed the field of oncology, tissue access is often limited in HCC and a single biopsy is poorly representative of the known tumor genetic heterogeneity. Liquid biopsy has emerged as a promising strategy for analyzing circulating tumor components including circulating tumor DNA. Cell-free DNA and tumor DNA are derived from necrotic, apoptotic and living eukaryotic cells. The profiling of genetic and epigenetic alterations in circulating cell-free DNA has potential clinical applications including early disease detection, prediction of treatment response and prognostication in real time. Novel biomarker candidates for disease detection and monitoring are under study. Of these, methylation analyses of circulating tumor DNA have shown promising performance for early HCC detection in at risk patients. Assessments of assay performance in longitudinal validation cohorts are ongoing. Implementation of liquid biopsy for HCC will likely improve upon the current surveillance strategy. This review summarizes the most recent developments on the role and utility of circulating cell-free DNA in the detection and management of HCC.