A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Early diagnosis and treatment of HCC remain a key goal for improving patient survival. Chronic hepatitis B virus (HBV) infection is a major risk factor for HCC development. Pre-S mutants harboring deletions...

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Autores principales:	Chiao-Fang Teng, Hsi-Yuan Huang, Tsai-Chung Li, Woei-Cherng Shyu, Han-Chieh Wu, Chien-Yu Lin, Ih-Jen Su, Long-Bin Jeng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Simple Kappa Coefficient Cancer-related Death Worldwide HBV E Antigen (HBeAg) HBV Surface Antigen (HBsAg) Low Detection Sensitivity Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c5011b5735bb42fd90994eecf15d6f47
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spelling	oai:doaj.org-article:c5011b5735bb42fd90994eecf15d6f472021-12-02T15:08:14ZA Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients10.1038/s41598-018-33051-42045-2322https://doaj.org/article/c5011b5735bb42fd90994eecf15d6f472018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33051-4https://doaj.org/toc/2045-2322Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Early diagnosis and treatment of HCC remain a key goal for improving patient survival. Chronic hepatitis B virus (HBV) infection is a major risk factor for HCC development. Pre-S mutants harboring deletions in HBV large surface antigen have been well demonstrated as HBV oncoproteins that dysregulate multiple signaling pathways in hepatocytes, leading to HCC formation. The presence of pre-S mutants in plasma represents important predictive and prognostic markers for HCC in patients with chronic HBV infection. However, the method to detect pre-S mutants remains to be optimized. In this study, we developed a platform, based on the next-generation sequencing (NGS) technology, for detection of pre-S mutants in plasma of HBV-related HCC patients. Compared to the current TA cloning-based analysis, the NGS-based analysis could detect pre-S deletion quantitatively, and the detection rate was significantly more sensitive in 49 plasma analyzed (McNemar’s paired proportion test, P value < 0.0001; simple kappa coefficient, κ = 0.29 (95% CI, 0.12 to 0.46)). Our data suggest that the NGS-based platform may hold a promise for improving the clinical application of pre-S mutants in serving as predictive and prognostic markers for HBV-related HCC.Chiao-Fang TengHsi-Yuan HuangTsai-Chung LiWoei-Cherng ShyuHan-Chieh WuChien-Yu LinIh-Jen SuLong-Bin JengNature PortfolioarticleSimple Kappa CoefficientCancer-related Death WorldwideHBV E Antigen (HBeAg)HBV Surface Antigen (HBsAg)Low Detection SensitivityMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Simple Kappa Coefficient Cancer-related Death Worldwide HBV E Antigen (HBeAg) HBV Surface Antigen (HBsAg) Low Detection Sensitivity Medicine R Science Q
spellingShingle	Simple Kappa Coefficient Cancer-related Death Worldwide HBV E Antigen (HBeAg) HBV Surface Antigen (HBsAg) Low Detection Sensitivity Medicine R Science Q Chiao-Fang Teng Hsi-Yuan Huang Tsai-Chung Li Woei-Cherng Shyu Han-Chieh Wu Chien-Yu Lin Ih-Jen Su Long-Bin Jeng A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
description	Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Early diagnosis and treatment of HCC remain a key goal for improving patient survival. Chronic hepatitis B virus (HBV) infection is a major risk factor for HCC development. Pre-S mutants harboring deletions in HBV large surface antigen have been well demonstrated as HBV oncoproteins that dysregulate multiple signaling pathways in hepatocytes, leading to HCC formation. The presence of pre-S mutants in plasma represents important predictive and prognostic markers for HCC in patients with chronic HBV infection. However, the method to detect pre-S mutants remains to be optimized. In this study, we developed a platform, based on the next-generation sequencing (NGS) technology, for detection of pre-S mutants in plasma of HBV-related HCC patients. Compared to the current TA cloning-based analysis, the NGS-based analysis could detect pre-S deletion quantitatively, and the detection rate was significantly more sensitive in 49 plasma analyzed (McNemar’s paired proportion test, P value < 0.0001; simple kappa coefficient, κ = 0.29 (95% CI, 0.12 to 0.46)). Our data suggest that the NGS-based platform may hold a promise for improving the clinical application of pre-S mutants in serving as predictive and prognostic markers for HBV-related HCC.
format	article
author	Chiao-Fang Teng Hsi-Yuan Huang Tsai-Chung Li Woei-Cherng Shyu Han-Chieh Wu Chien-Yu Lin Ih-Jen Su Long-Bin Jeng
author_facet	Chiao-Fang Teng Hsi-Yuan Huang Tsai-Chung Li Woei-Cherng Shyu Han-Chieh Wu Chien-Yu Lin Ih-Jen Su Long-Bin Jeng
author_sort	Chiao-Fang Teng
title	A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
title_short	A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
title_full	A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
title_fullStr	A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
title_full_unstemmed	A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients
title_sort	next-generation sequencing-based platform for quantitative detection of hepatitis b virus pre-s mutants in plasma of hepatocellular carcinoma patients
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c5011b5735bb42fd90994eecf15d6f47
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A Next-Generation Sequencing-Based Platform for Quantitative Detection of Hepatitis B Virus Pre-S Mutants in Plasma of Hepatocellular Carcinoma Patients

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