Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death.
The initiation of protein translation is an important rate-limiting step in eukaryotes,
and is crucial in the pathogenesis of many viral infections. Eukaryotic translation
initiation factors (eIFs) are proteins that are involved in the initiation step of
protein translation and are linked to the phosphatidylinositol-3-kinases (PI3K)/AKT/mTOR
pathway. We hypothesized that eIFs represent crossroads for carcinogenesis in HCC
and might serve as potential biomarkers. The immunohistochemical expression of eIF
subunits 2α, 3C, 3 H, 4E, 5 and 6 were investigated in 235 cases of virus-related
human HCCs. Additionally, we used immunoblot analysis to investigate the expression
of virus-related HCC and non-virus-related HCC in comparison to controls. mTOR pathway
members were significantly increased in HCV-associated HCC, in HCC without a viral
background, in alcoholic liver disease and Wilson's disease. peIF2α, eIF2α, eiF3B,
eIF3D, eIF3J, peIF4B, eIF4G and eIF6 were upregulated in HCV-associated HCC. eIF2α,
peIF4B, eIF5 and various eIF3 subunits were significantly increased in HBV-associated
HCC. HCC without viral background displayed a significant increase for the eIF subunits
p2α, 3C, 3I, 4E and 4G. We noticed engraved differences in the expression pattern
between chronic hepatitis B and C, HBV- and HCV associated HCC and non-virus related
HCC. Our data demonstrate that mTOR members and eIFs play a crucial role in translational
control in chronic hepatitis B and C, HBV- and HCV-associated HCC and non-virus related
HCC and therefore serve as novel potential biomarkers.
