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Application of HBx-induced anti-URGs as early warning biomarker of cirrhosis and HCC

Article type: Research Article

Authors: Wang, Wena; 1 | Zhao, Lan-Juana; 1 | Wang, Yana; 1 | Tao, Qing-Yuana | Feitelson, Mark A.a; b | Zhao, Pinga | Ren, Haoa | Qi, Zhong-Tiana; *

Affiliations: [a] Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, China | [b] Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA

Correspondence: [*] Corresponding author: Hao Ren, Department of Microbiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Tel./Fax: +86 21 81870988; E-mail: [email protected]; Zhong-Tian Qi, Department of Microbiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Tel./Fax: +86 21 81870988; E-mail: [email protected] E-mail: [email protected]; Zhong-Tian Qi, Department of Microbiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China. Tel./Fax: +86 21 81870988; E-mail: [email protected].

Note: [1] These three authors contributed equally to this work.

Keywords: Anti-URGs, Hepatocellular carcinoma, hepatitis B virus x antigen, biomarker, early diagnosis

DOI: 10.3233/CBM-2012-0261

Journal: Cancer Biomarkers, vol. 11, no. 1, pp. 29-39, 2012

Published: 11 July 2012
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Abstract

Background:

Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk patients. HBV up-regulates the expression of selected genes (URGs) in the liver during chronic infection. These aberrantly expressed proteins trigger corresponding antibodies (anti-URGs) that appear prior to the detection of HCC. This study was undertaken to see if the anti-URGs could be used as early warning biomarker of HBV-induced liver cirrhosis and HCC.

Methods:

A cross sectional study using a total of 625 serum samples from HBV infected and uninfected controls were tested for the anti-URGs using specific ELISAs.

Results:

The number and specificity of anti-URGs correlated with the severity of liver disease Anti-URGs were predominantly present among patients with HBV-associated HCC (55.2%) and cirrhosis (60.7%), and at a lower frequency among patients with chronic hepatitis (35.8%), and at still lower frequencies in most asymptomatic carriers (12.3%) with normal ALT, among patients with chronic hepatitis C (38.5%) and blood donors (0.9%). These anti-URGs were rarely detected in sera from those with tumors other than HCC, except among HBV infected patients with cholangioicarcinoma and in some patients with drug induced hepatitis. 3 or more anti-URGs could precede the diagnosis of cirrhosis or HCC 11.8 months on average, and HBV hepatitis patients with 3 or more anti-URGs have much higher risk (5/20 vs 0/30) to develop cirrhosis and HCC than those patients with less anti-URGs. As the early warning biomarker, 3 or more anti-URGs were served as the threshold to separate the cirrhosis and HCC from others with a moderate sensitivity (58.3%) and specificity (80.0%), which was better than other biomarkers (AFP, AFP-L3, GPC3 and GP73) and would improve up to 70.3% when combined with another biomarker.

Conclusions:

The results of this clinical validation study suggest that the anti-URGs might have diagnostic/prognostic utility among patients at high risk for the development of cirrhosis and HCC.

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