Alcoholic versus Non‐alcoholic Steatohepatitis: Levels of Expression of Some Proteins Involved in Tumorigenesis

Abstract

Non‐alcoholic steatohepatitis (NASH) is commonly associated with obesity, type 2 diabetes, and/or hypertriglyceridemia, while alcoholic steatohepatitis (ASH) is associated with alcohol abuse. Both NASH and ASH patients can develop cirrhosis and hepatocellular carcinoma if left untreated. However, the rate of tumorigenesis in NASH and ASH appears to be different. Individuals with NASH progress to cirrhosis at a rate of 7–10% annually, when individuals with ASH progress to cirrhosis at a rate of 10–20% annually. Thus, the objective of our study is to determine if there are differences in NASH versus ASH in the levels of different proteins expressed involved in cancer development. The method used was measuring the proteins expressed in liver biopsied sections from NASH and ASH patients using immunohistochemical staining with fluorescent antibodies and then quantitating the fluorescence intensity morphometrically. Normal liver biopsies were used as controls. The 20 proteins tested were parts of the Ingenuity Canonical Pathway of Molecular Mechanisms of Cancer and included: RAP2B, NAIP, FYN, PAK6, SUV39H1, GNAI1, BAX, E2F3, CKDN2B, BAK1, BCL2, DIABLO, RASGRF2, GNA15, PIK3CB, BRCA1, MAP2K1, BIRC3, CDK2, and ATM. For the results, in ASH, the proteins which had upregulated levels of expression were SUV39H1, E2F3, BCL2, BAK1, BIRC3, and GNAI1. In NASH, the proteins which had upregulated levels of expression were BAK1 and GNAI1 and the one which had downregulated levels of expression was BCL2. Additionally, the levels of expression for SUV39H1, E2F3, BCL2, BAK1, BIRC3 and GNAI1 were significant upregulated in ASH compared to NASH. These results showed significant differences in ASH compared to normal liver, and significant differences in ASH compared to NASH. We conclude that there are more proteins involved in tumorigenesis in ASH compared to NASH and normal liver, which is consistent with the known tumor development rate in ASH and NASH.Support or Funding InformationThis study was funded by NIH:NIAAA grant # UO1‐021898‐05This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.