Different Roles of Epigenetic Regulators and Inflammasome in Hepatocellular Carcinoma Tumorigenesis in Patients with ASH vs. NASH

Abstract

As the fifth most common cancer and the second leading cause of cancer related deaths worldwide, hepatocellular carcinoma (HCC) is an aggressive tumor type with poor prognosis causing 250,000 to one million deaths annually. Alcoholic steatohepatitis (ASH) and non‐alcoholic steatohepatitis (NASH) are the two major growing risk factors and both may develop liver fibrosis or even HCC. However, compared with the rate of patients with ASH progressing to HCC annually, it is much lower in NASH patients. The present study is to clarify the protein expression of epigenetic regulators and Inflammasome components in the oncogenesis pathway between ASH and NASH. By using the immunofluorescence method and morphometrically quantitating the fluorescence intensity in liver biopsied specimens from NASH and ASH patients, we studied the protein expression within hepatocytes cytoplasm of candidate epigenetic regulators G9A and LHPP and inflammasome component ASC. Compared with the control group patients, the expression levels of all three proteins were upregulated in the ASH and NASH group of patients (p < 0.001 in all molecules). While compared with the ASH group of patients, only the expression levels of G9A were significantly lower in the NASH group of patients (p < 0.01). The other two molecules, LHPP and ASC did not change. These results are consistent with our previous work that there are significant differences of many molecules including epigenetic modulators and the inflammasome pathway in both NASH and ASH compared to the control group. Thus, we conclude that there are significantly different molecules and pathways involved during the pathogenesis of HCC development in NASH compared to ASH which may focus the light on developing prevention methods and targeted treatments in NASH and ASH patients.Support or Funding InformationThis study was funded by NIH/AAA grant # UO‐21898‐05.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.