Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is associated with repression of interferon regulatory factor-1.
OBJECTIVE
Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus infection results in activation or direct induction of the interferon regulatory factors (IRFs), which are a family of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been shown to play an essential role in virus-dependent signaling, whereas IRF-1 is critical for proper IFN-dependent gene expression. This study has been performed to show the expression profile of IRF-1, IRF-3, and IRF-7 in Egyptian patients with HCV-related liver diseases and hepatocellular carcinoma (HCC).


METHODS
This study included 90 patients, who were positive for HCV infection by reverse transcription PCR, divided into three groups: group I (Gr I) included 30 patients with chronic hepatitis C, group II (Gr II) included 30 patients with liver cirrhosis in addition to group III (Gr III) of 30 patients with HCC. Reverse transcription PCR analysis was performed to determine the expression profile of IRF-1, IRF-3, and IRF-7 genes extracted from the peripheral blood mononuclear cells of those patients.


RESULTS
IRF-1expression was significantly higher (P<0.001) in patients of Gr I (86.6%) compared with those in Gr II (46.7%) and Gr III (36.7%), whereas IRF-3 expression was significantly higher (P<0.005) among patients of Gr II (73.3%) in comparison with that in Gr I (50%) and Gr III (36.7%). In contrast, although expression of IRF-7 was higher in Gr II than in the other groups, there was no statistically significant difference (P > 0.05).


CONCLUSIONS
Alterations in IRFs expression might be considered as markers associated with a higher risk of cirrhosis in patients with chronic HCV infection. Expression of IRF-1 and IRF-3 were more prevalent in patients with chronic HCV and cirrhosis, respectively, in comparison with HCC patients. Thus, IRF-1 could be nominated as one of the tumor suppressor factors and could aid in the early detection of HCC.
Zekri
Abdel-Rahman N
AR
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt. ncizekri@yahoo.com
Moharram
Rabab A N
RA
Mohamed
Waleed S
WS
Bahnassy
Abeer A
AA
Alam El-Din
Hanaa M
HM
Abo-Shadi
Maha M
MM
Zayed
Naglaa A
NA
El-Magzangy
Husseim
H
Abdel-Aziz
Ashraf O
AO
Esmat
Gamal
G
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002908:Chronic Disease; D018450:Disease Progression; D004534:Egypt; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000378:metabolism; D007372:Interferons / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D050856:Interferon Regulatory Factor-1; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007372:Interferons