Expression of pro- and anti-inflammatory cytokines in relation to apoptotic genes in Egyptian liver disease patients associated with HCV-genotype-4.
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 (TNFalpha, TNF-RI, TNF-RII, IL-6, IL-6R), anti-inflammatory IL-10, CRP and alphaFP 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-3beta, TNFalpha, 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, TNFalpha and TNFRI. A significant relation was observed between cirrhosis and GSK-3beta, 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.
Zekri
Abdel-Rahman N
AR
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. ncizekri@yahoo.com
Bahnassy
Abeer A
AA
Abdel-Wahab
Sabrin A
SA
Khafagy
Medhat M
MM
Loutfy
Samah A
SA
Radwan
Hessam
H
Shaarawy
Sabry M
SM
D000368:Aged; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics*; D004534:Egypt; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000208:ethnology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D014408:Biomarkers, Tumor; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger