Oncotarget

Clinical Research Papers:

Interferon-stimulated gene 20 kDa protein serum levels and clinical outcome of hepatitis B virus-related liver diseases

Hoang Van Tong, Nghiem Xuan Hoan, Mai Thanh Binh, Dao Thanh Quyen, Christian G. Meyer, Le Huu Song, Nguyen Linh Toan and Thirumalaisamy P. Velavan _

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Oncotarget. 2018; 9:27858-27871. https://doi.org/10.18632/oncotarget.25559

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Abstract

Hoang Van Tong1,2,3, Nghiem Xuan Hoan3,4,5, Mai Thanh Binh3,4,5, Dao Thanh Quyen3,4,5, Christian G. Meyer3,5,6, Le Huu Song4,5, Nguyen Linh Toan2 and Thirumalaisamy P. Velavan3,5,6

1Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Vietnam

2Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam

3Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

4108 Military Central Hospital, Hanoi, Vietnam

5Vietnamese-German Center of Excellence in Medical Research, Hanoi, Vietnam

6Duy Tan University, Da Nang, Vietnam

Correspondence to:

Hoang Van Tong, email: hoangvantong@vmmu.edu.vn

Thirumalaisamy P. Velavan, email: velavan@medizin.uni-tuebingen.de

Keywords: interferon-stimulated gene; ISG20 levels; ISG20 expression; viral hepatitis; hepatocellular carcinoma

Received: April 10, 2018    Accepted: May 21, 2018    Published: June 12, 2018

ABSTRACT

Interferon-stimulated gene 20 kDa protein (ISG20) with 3’ to 5’ exonuclease activity mainly targeting single-stranded RNA plays an important role in immune responses against various infectious pathogens, including hepatitis viruses. ISG20 levels were measured by ELISA assays in sera of 339 hepatitis B-virus (HBV) infected patients and 71 healthy individuals and were correlated with clinical and laboratory parameters. ISG20 mRNA was quantified by qRT-PCR in 30 pairs of hepatocellular carcinoma (HCC) tumour and adjacent non-tumour liver tissues. ISG20 levels were significantly elevated in HBV patients compared to healthy controls (P<0.0001). In the patient group, varying ISG20 levels were associated with different forms of HBV-related liver diseases. ISG20 levels were higher in patients with HCC compared to those without HCC (P<0.0001), and increased according to the stages of HCC (P<0.0001). ISG20 mRNA expression was up-regulated in tumour tissues compared to the expression in adjacent non-tumour tissues (P=0.017). Importantly, ISG20 levels were strongly correlated with the levels of AST, ALT, total and direct bilirubin among HCC patients (Pearson’s r = 0.43, 0.35, 0.34, 0.3; P<0.0001, respectively). Although differences between liver cirrhosis (LC) and non-LC patients were not observed, ISG20 levels were elevated according to the progression of cirrhosis in patients with LC plus HCC (P=0.005). In conclusions, ISG20 levels are induced by HBV infection and significantly associated with progression and clinical outcome of HBV-related liver diseases, especially in patients with HCC. ISG20 might be a potential indicator for liver injury and the clinical outcome in HBV-related HCC.


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