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

Chiao-Fang Teng,Hsi-Yuan Huang,Woei-Cherng Shyu,Wen-Shu Chen,Cheng-Yuan Peng,Long-Bin Jeng,Han-Chieh Wu,Tsai-Chung Li,Jia-Hui Lin,Ih-Jen Su

doi:10.3390/v12080796

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is the sixth most frequent human cancer and the second leading cause of cancer-related death worldwide, responsible for around 740,000 deaths in 2012 [1,2,3].Many therapeutic strategies have been developed for the treatment of HCC, among which surgical resection is regarded as one of the best therapeutic options for HCC patients [4,5,6,7]
We have recently developed a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in plasma samples of Hepatitis B virus (HBV)-related HCC patients with better sensitivity and accuracy [25,26]. We further evaluated this NGS-based quantitative detection of pre-S mutants as a powerful approach to predict HCC recurrence in HBV-related HCC patients receiving surgical resection
To investigate the association of preoperative pre-S deletions with median overall survival (OS) and recurrence-free survival (RFS), the plasma samples were obtained retrospectively from 75 HBV-related HCC patients on the day of the surgical resection they received at China Medical

Summary

Introduction

Hepatocellular carcinoma (HCC) is the sixth most frequent human cancer and the second leading cause of cancer-related death worldwide, responsible for around 740,000 deaths in 2012 [1,2,3].Many therapeutic strategies have been developed for the treatment of HCC, among which surgical resection is regarded as one of the best therapeutic options for HCC patients [4,5,6,7]. Hepatocellular carcinoma (HCC) is the sixth most frequent human cancer and the second leading cause of cancer-related death worldwide, responsible for around 740,000 deaths in 2012 [1,2,3]. The recurrence rate of HCC after curative surgical resection is up to 80% within five years, leading to a poor patient survival rate as low as 30% within five years [8,9,10]. Chronic infection with hepatitis B virus (HBV) is a major risk factor for HCC development, accounting for over 50% of total HCC cases in developing countries [11,12]. We have identified ground glass hepatocytes (GGHs) in liver tissues as a histological marker of chronic

Methods

Results

Conclusion