engleski

NF-κB, Nuclear EGFR and cyclin D1 in pathogenesis of HCV mediated liver disease

INTRODUCTION: Several lines of evidence indicate a strong causal association between chronic hepatitis C (CHC) and hepatocellular carcinoma (HCC). Hepatocytes are the primary site of HCV replication. The molecular events during hepatocytes proliferation are related closely to the cell cycle and its regulation. NF-κB activates a large group of genes which encodes proteins involved in immune response, production of proinflammatory cytokines and regulators of cell proliferation. EGFR plays a central role in the tumorigenesis and malignance biology of many human cancers. Cyclin D1 protein is involved in G1/S cell cycle transition. Nuclear EGFR associates with cyclin D1 gene promoter and functions as a transcription factor that activates cyclin D1 gene expression. AIM of this study was to evaluate the role and significance of NF-κB protein expression in liver tissue of patients with CHC and correlate the clinical and histopathological assessment of liver lesions with molecular biomarkers that indicate cell regeneration and proliferation (EGFR, cyclin D1 and proliferation marker Ki-67). MATERIAL AND METHODS: Tissue microarrays (TMAs) were built from 80 archival formalin fixed paraffin embedded needle liver biopsies obtained from patients with confirmed chronic hepatitis C, as a part of regular diagnostic protocol. Immunohistochemistry was performed for NF-κB, nuclear EGFR, cyclin D1 and Ki-67. RESULTS: Increased expression of NF-κB in the nuclei of hepatocytes is associated with severity of hepatitis (p=0, 047), thus suggesting its role as proinflammatory mediator. Protein expression of nuclear EGFR is associated with grade of hepatitis (p=0, 0013) and directly correlated with increased expression of cyclin D1 (p<0, 0001), indicating its function as promoter of hepatocyte proliferation. CONCLUSION: Evaluation of the expression of proteins related to cell cycle and cellular growth in patients with CHC and HCC will help in identification of new molecular biomarkers involved in virus-induced liver damage and the carcinogenic processes.

NF-κB; Nuclear EGFR; cyclin D1; hepatitis; hepatocellular carcinoma

nije evidentirano