Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: I- HCV promotes HCC progression by increasing cancer stem marker (CD133 and CD44) expression

Abstract

Hepatitis C virus (HCV) represents a major public health problem, affecting 3% of the world’s population. In majority of infected patients, HCV can effectively evade innate immunity resulting in chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma (HCC). Similar to most solid tumors, HCCs are believed to contain poorly differentiated cancer stem cell-like cells (CSCs) that initiate tumorigenesis and confer resistance to chemotherapy. The present work attempted to study the mRNA expression of cancer stem cell markers (CD133 and CD44) in patients with chronic hepatitis C virus (reflecting the role of HCV) and their correlation with progression toward cirrhosis and HCC. Peripheral blood mononuclear cell (PBMC) prepared from chronic HCV patients (either with or without complications) were probed for mRNA expression of CD133 and CD44 by RT-PCR and compared to that of non-HCV cirrhotic patients as well as healthy control subjects. Our results showed that mRNA expression of CD133 was significantly elevated in all HCV patients either with or without complications but not in those with non-HCV cirrhosis, with maximal expression in patients without complications (HCV patients only). On the other hand, maximal CD44 mRNA expression was recorded in HCC patients. Taken together, these results suggests that, chronic HCV infection appear to predispose cells towards the path of acquiring cancer stem cell traits by inducing CD133 and CD44 expression and it prove the hypothesis that the viral interference with signaling network of normal stem cells leads to their transformation into CSCs.