OC-029 Expression of heat shock protein 27 and caspase-3 in hepatitis C virus-related hepatocellular carcinoma: relation to tumour progression

Abstract

Introduction Hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC), however, the mechanism of hepatocarcinogenesis in HCV infection is still undefined. Heat shock protein (HSP) 27 is a ubiquitous chaperone molecule induced in cells exposed to different stress conditions, including carcinogenesis. It also has potent anti-apoptotic properties through inhibition of caspase-3 activation. Therefore, the aim of the present work was to study the expression of HSP27 and caspase-3 in HCV-related HCCs in relation to tumour progression. Methods Twenty cirrhotic patients with HCV-related HCC were enrolled in the study. The severity of liver disease was assessed according to the Model for End Stage Liver Disease (MELD) score. Serum levels of α-fetoprotein (AFP) were measured by enzyme immunoassay kit. The tumour stage was classified using the scoring system proposed by the Cancer of the Liver Italian Program (CLIP). Histological grading of tumour s was performed according to the Edmondson and Steiner9s criteria and the surrounding liver tissue was examined for the presence of cirrhosis and steatosis. Expression of HSP27 and caspase-3 was studied in HCC and adjacent non-neoplastic liver tissues by immunohistochemistry and the staining intensity of the tumour was designated as “negative/low expression” or “high expression” if 25% of cells were positively-stained, respectively. Results HCV-related HCCs showed a significant increase in HSP27 expression and a significant decrease in caspase-3 expression as compared with adjacent non-neoplastic liver tissues (p=0.029 and p=0.040, respectively). The expression of HSP27 showed an inverse correlation with caspase-3 expression in HCC tissues (r=−0.691, p=0.001). High HSP27 expression and negative/low caspase-3 expression in HCCs were associated with significant increases in serum levels of aminotransferases, HCV RNA and AFP, MELD score, tumour size, tumour stage, histological tumour grade, body mass index and the presence of steatosis in the surrounding liver tissue (P 0.05). Conclusion HSP27 plays an important role in the pathogenesis and progression of HCC in HCV infection through inhibition of caspase-3 mediated cell apoptosis and may serve as a potentially useful therapeutic target.