Abstract
BackgroundProtein kinase RNA (PKR-regulated) is a double-stranded RNA activated protein kinase whose expression is induced by interferon. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. However, it is possible that the function of PKR varies with the type of cancer in question.MethodsWe report here a detailed study to evaluate the function of PKR in hepatitis C virus genotype 4 (HCV-4) infected patients. PKR gene was quantitated in HCV related malignant and non-malignant liver tissue by RT-PCR technique and the association of HCV core and PKR was assessed.ResultsIf PKR functions as a tumour suppressor in this system, its expression would be higher in chronic hepatitis tissues. On the contrary our study demonstrated the specific association of HCV-4 with PKR expressed in hepatocellular carcinoma (HCC) tissues, leading to an increased gene expression of the kinase in comparison to chronic hepatitis tissues. This calls into question its role as a tumour suppressor and suggests a positive regulatory role of PKR in growth control of liver cancer cells. One limitation of most of other studies is that they measure the levels rather than the quantitation of PKR gene.ConclusionThe findings suggest that PKR exerts a positive role in cell growth control of HCV-4 related HCC, obtaining a cut-off value for PKR expression in liver tissue provides the first evidence for existence of a viral activator of PKR.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1267826959682402.
Highlights
Chronic infection with hepatitis C virus (HCV) is the predominant aetiology for the development of hepatocellular carcinoma (HCC) worldwide [1,2,3]
A very highly statistically significant elevated median level of alpha fetoprotein (AFP) was obtained in patients with hepatitis C virus genotype 4 (HCV-4) related HCC as compared with the other two groups (P < 0.0001)
We found that higher Protein kinase Ribonucleic acid (RNA) regulated (PKR) gene expression was associated with higher scores of fibrosis and histological activity index (HAI) in both HCV-4 and HCV-4 related HCC cases
Summary
Chronic infection with hepatitis C virus (HCV) is the predominant aetiology for the development of hepatocellular carcinoma (HCC) worldwide [1,2,3]. HCV accounts for about 70% of cases with chronic hepatitis, 40% with cirrhosis, 60% with HCC and 15-30% of liver transplantation [4,5]. The prevalence of HCV infection varies throughout the world, the highest number of worldwide, with a 5 year survival rate of less than 5% [9]. The genes involved are implicated in cell proliferation and apoptosis [11,12]. The role of PKR in cell growth regulation is controversial, with some studies supporting a tumour suppressor function and others suggesting a growth-promoting role. It is possible that the function of PKR varies with the type of cancer in question
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