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Keywords:

  • Cytokines;
  • apoptosis;
  • genes;
  • HCV-4;
  • liver;
  • disease;
  • RT-PCR

Abstract

Background:  Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide strongly linked to hepatitis C virus (HCV) infection. However, the exact pathogenetic mechanisms are still unclear.

Methods:  We assessed the expression of apoptosis genes (GSK3-B, AKT-1, Bcl-2), inflammatory cytokines (TNFα, TNF-RI, TNF-RII, IL-6, IL-6R), anti-inflammatory IL-10, CRP and αFP by reverse transcription—polymerase chain reaction (RT-PCR) in 33 HCC, 25 chronic hepatitis and 16 asymptomatic HCV carrier positive for HCV subjects. Also, pooled normal liver tissues and HepG2 cells were used as controls.

Results:  Hepatocellular carcinoma and liver disease (LD) showed reduced expression of GSK-3β, TNFα, TNF-R I, TNF-RII, IL-10 and overexpression of IL-6R and CRP with no significant difference between the two groups. AFP was expressed in HCC only (33%). AKT, BCL2 and IL-6 showed normal, reduced and overexpression in studied patients with a significant difference between AFP, AKT overexpression (67% and 30%), BCL2 overexpression (49% and 10%) and reduced IL-6 in between HCC and LD. The morphologically normal tissues adjacent to tumors showed aberrant expression of AKT, IL-6, CRP, TNFα and TNFRI. A significant relation was observed between cirrhosis and GSK-3β, AKT and IL-6 (P = 0.0018, P = 0.018, P = 0.0001; respectively).

Conclusions:  Aberrant expressions of AKT, GSK3-B, and BCL2 are common events in HCV-associated LD and HCC. AKT, GSK3-B and IL-6 are significantly associated with cirrhosis and could be used as biomarkers for both early detection and molecular target therapy for the prevention of HCC development. TNFRII, GSK3-B and s-AFP could be used as prognostic factors that can predict the clinical outcome of HCC patients.