Van Tong Hoang, Hoan Nghiem Xuan, Binh Mai Thanh, Quyen Dao Thanh, Meyer Christian G, Song Le Huu, Toan Nguyen Linh, Velavan Thirumalaisamy P
Institute of Biomedicine and Pharmacy, Vietnam Military Medical University, Hanoi, Vietnam.
Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Oncotarget. 2018 Jun 12;9(45):27858-27871. doi: 10.18632/oncotarget.25559.
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. 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 (<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 (<0.0001), and increased according to the stages of HCC (<0.0001). ISG20 mRNA expression was up-regulated in tumour tissues compared to the expression in adjacent non-tumour tissues (=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; <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 (=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.
干扰素刺激基因20千道尔顿蛋白（ISG20）具有主要针对单链RNA的3'至5'核酸外切酶活性，在针对包括肝炎病毒在内的各种传染性病原体的免疫反应中发挥重要作用。通过酶联免疫吸附测定（ELISA）检测了339例乙型肝炎病毒（HBV）感染患者和71例健康个体血清中的ISG20水平，并将其与临床和实验室参数相关联。通过定量逆转录聚合酶链反应（qRT-PCR）对30对肝细胞癌（HCC）肿瘤组织和相邻的非肿瘤肝组织中的mRNA进行了定量分析。与健康对照相比，HBV患者的ISG20水平显著升高（<0.0001）。在患者组中，不同的ISG20水平与不同形式的HBV相关肝病有关。与无HCC的患者相比，HCC患者的ISG20水平更高（<0.0001），并且根据HCC的阶段而升高（<0.0001）。与相邻非肿瘤组织中的表达相比，肿瘤组织中ISG20 mRNA表达上调（=0.017）。重要的是，HCC患者中ISG20水平与天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、总胆红素和直接胆红素水平密切相关（Pearson相关系数r分别为0.43、0.35、0.34、0.3；均<0.0001）。虽然未观察到肝硬化（LC）患者和非LC患者之间的差异，但在合并HCC的LC患者中，ISG20水平随肝硬化进展而升高（=0.005）。总之，ISG20水平由HBV感染诱导，并与HBV相关肝病的进展和临床结局显著相关，尤其是在HCC患者中。ISG20可能是HBV相关HCC肝损伤和临床结局的潜在指标。
