Prognostic Liver Signature for NAFLD (PLS-NAFLD) profiles of cell-based PLS system treated with free fatty acids (FFA) and IDO1 inhibitor, epacadostat.

Non-alcoholic fatty liver disease (NAFLD), alongside the global obesity epidemic, is rapidly emerging as a dominant liver disease etiology that leads to progressive liver fibrosis, its terminal stage, cirrhosis, and hepatocellular carcinoma (HCC). We identified and validated a 133-gene signature (Prognostic Liver Signature for NAFLD [PLS-NAFLD]) to predict long-term HCC risk in patients with NAFLD. By analyzing PLS-NAFLD, IDO1 was identified as a potenial chemopreventive target for HCC from NAFLD. To test this hypothesis, we utilized our clinical-prognostic-signature-inducible cell culture model. We first confirmed that free fatty acid treatment (800 μM oleic acid and 400 μM palmitic acid) can induce PLS-NAFLD, then IDO1 inhibitor, epacadostat, can reverse the high-risk pattern in a dose-dependent manner. Co-cultuered DMSO-differentiated Huh7.5.1 cells (Huh7.5.1dif) and LX2 cell were exposed to FFA (800 μM oleic acid and 400 μM palmitic acid) or mock, then treated with IDO1 inhibitor, epacadostat, or DMSO to maesure modulation of Prognostic Liver Signature for NAFLD.