<p class="first" id="P1">Hepatocellular carcinoma (HCC) is the fifth most common cancer
and the second leading
cause of cancer related deaths worldwide. Among others, non-alcoholic steatohepatitis
(NASH) and alcoholic steatohepatitis (ASH) are the two major risk factors as both
of them may develop cirrhosis and hepatocellular carcinoma (HCC) if left untreated.
However, patients with NASH progress to HCC at a rate around 0.5% annually, while
3–10% ASH patients may progress to HCC annually. The present study is to demonstrate
the molecular differences in oncogenesis pathway between NASH and ASH. By using immunofluorescence
study and quantitating the fluorescence intensity morphometrically in liver biopsied
specimens from NASH and ASH patients, the protein expression of candidate molecules
within hepatocytes cytoplasm are studied, including two HCC-related molecules FAT10
and FOXO1, and one GPCR pathway related molecule ADRA2A. Compared with the control
group patients, the expression levels of all the molecules were upregulated in the
ASH group of patients(p<0.001 in all molecules), while FAT10 and ADRA2A were upregulated,
FOXO1 did not change in the NASH group of patients.The most important finding is that
compared with the ASH group of patients, the expression levels of all three molecules
were significantly lower than in the NASH group of patients (p<0.001 in all molecules).
These results confirmed our previous finding that there are significant differences
of molecules change in ASH compared to NASH. Thus, we conclude that there are significantly
different molecules and pathways involved during the pathogenesis of HCC development
in ASH compared to NASH which could help explain why the tumorigenic rate is different
in ASH and NASH.