Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4
Version of Record online: 27 NOV 2008
© 2008 The Authors. Journal compilation © 2008 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 24, Issue 3, pages 416–428, March 2009
How to Cite
Zekri, A.-R. N., Bahnassy, A. A., Abdel-Wahab, S. A., Khafagy, M. M., Loutfy, S. A., Radwan, H. and Shaarawy, S. M. (2009), Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4. Journal of Gastroenterology and Hepatology, 24: 416–428. doi: 10.1111/j.1440-1746.2008.05699.x
- Issue online: 23 MAR 2009
- Version of Record online: 27 NOV 2008
- Accepted for publication 3 September 2008.
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.