Next-Generation Sequencing-Based Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma Predicts Hepatocellular Carcinoma Recurrence

• Published in: Viruses Vol. 12; no. 8; p. 796
• Main Authors: Teng, Chiao-Fang, Li, Tsai-Chung, Huang, Hsi-Yuan, Lin, Jia-Hui, Chen, Wen-Shu, Shyu, Woei-Cherng, Wu, Han-Chieh, Peng, Cheng-Yuan, Su, Ih-Jen, Jeng, Long-Bin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.07.2020; MDPI
• Subjects: Adult; Aged; Biomarkers; Capsid Proteins - blood; Capsid Proteins - genetics; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - virology; Cloning; Deoxyribonucleic acid; DNA; Female; Gene Deletion; Genotype; Genotype & phenotype; Hepatitis; Hepatitis B; hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - virology; Hepatocellular carcinoma; High-Throughput Nucleotide Sequencing; Humans; Infections; Liver cancer; Liver Neoplasms - blood; Liver Neoplasms - virology; Male; Medical prognosis; Middle Aged; Mutants; Mutation; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - virology; Next-generation sequencing; Patients; Plasma; pre-S mutants; Prognosis; Proteins; recurrence; Retrospective Studies; Survival; United States > US; China; recurrence; next-generation sequencing; hepatitis B virus; hepatocellular carcinoma; pre-S mutants
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v12080796

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner.