Plasma Circulating Tumor DNA Sequencing Reveals the Landscape of Acquired Mutations in Patients with Hepatocellular Carcinoma: a Potential Predictive Value in Liquid Biopsy

Abstract Background Recent advances in circulating tumor DNA (ctDNA) analysis offer a promising approach for diagnosing and monitoring hepatocellular carcinoma (HCC). This study focused on the potential clinical role of ctDNA analysis in HCC management. Materials and methods: Thirty patients with HCC and 10 with non-malignant liver disease were enrolled in this study. Circulating free nucleic acids, germline DNA, and tumor DNA (tDNA) from both blood samples and paraffin-embedded tumor biopsies were analyzed by a panel targeting 100 common HCC-related genes. Results The ctDNA mutations were identified in 66.6% of HCC patients. New ctDNA mutations were identified, among them NCOR2 having the highest frequency (13%), the same with classical mutation CTNNB1. Gene sets composed of several mutations in ctDNA have the potential to predict the prognosis of HCC. A higher proportion of concordant mutations was also detected in HCC patients with tumor vascular invasion (p=0.045). Combining the ctDNA mutations and the Alpha-fetoprotein (AFP) level revealed more diagnostic accuracy than either the mutations or AFP alone, with p-values of 0.028 and 0.009, respectively. Conclusion Liquid biopsy-based analysis of ctDNA mutations may offer considerable benefits to diagnostic systems for HCC.