Abstract
This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.
Highlights
Effective vaccines for hepatitis B virus (HBV) infections are available, HBV-related liver diseases remain a health problem of considerable concern with 250 million chronic carriers globally [1]
According to Barcelona Clinic Liver Cancer (BCLC) staging [25], 25/36 (69%) hepatocellular carcinoma (HCC) patients were in stage A and 11/36 (31%) HCC patients in stage B
We examined whether Interferon-stimulated gene 15 (ISG15) mRNA expression can be up-regulated during HCC development, ISG15 mRNA expression did not differ between stage A and stage B HCC tissues (Figure 4B)
Summary
Effective vaccines for hepatitis B virus (HBV) infections are available, HBV-related liver diseases remain a health problem of considerable concern with 250 million chronic carriers globally [1]. In Vietnam, the prevalence of HBV infection currently ranges from 10% to 20% in general population and HBV-related liver diseases are foreseen and predicted to be a notable public health burden in the decades [2]. HBV causes various forms of infection, ranging from an asymptomatic carrier status to liver cirrhosis (LC) and life-threatening hepatocellular carcinoma (HCC) [1]. Important factors influencing disease progression include the patient’s age, duration of HBV infection, and host-virus interactions. IFN-α mediates signal transduction by binding to its receptors. Tyrosine phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 leads to the formation www.impactjournals.com/oncotarget
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