Plasma proteome profiling discovers novel proteins associated with non‐alcoholic fatty liver disease

TLDR

Non‑alcoholic fatty liver disease affects a quarter of the population, can progress to cirrhosis, and alters the plasma proteome because the liver secretes most blood proteins, with enzymes such as DPP4, ANPEP, and TGFBI up‑regulated and implicated in fibrosis. Plasma proteome profiling can identify potential biomarkers and drug targets in liver disease. Proteomic analysis of 48 patients revealed six proteins with significant changes, including PIGR, which rose 170 % in NAFLD and 298 % in cirrhosis and was validated in mice, and a correlation map linked DPP4, ANPEP, TGFBI, PIGR, and APOE to liver disease.

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population and can progress to cirrhosis with limited treatment options. As the liver secretes most of the blood plasma proteins, liver disease may affect the plasma proteome. Plasma proteome profiling of 48 patients with and without cirrhosis or NAFLD revealed six statistically significantly changing proteins (ALDOB, APOM, LGALS3BP, PIGR, VTN, and AFM), two of which are already linked to liver disease. Polymeric immunoglobulin receptor (PIGR) was significantly elevated in both cohorts by 170% in NAFLD and 298% in cirrhosis and was further validated in mouse models. Furthermore, a global correlation map of clinical and proteomic data strongly associated DPP4, ANPEP, TGFBI, PIGR, and APOE with NAFLD and cirrhosis. The prominent diabetic drug target DPP4 is an aminopeptidase like ANPEP, ENPEP, and LAP3, all of which are up-regulated in the human or mouse data. Furthermore, ANPEP and TGFBI have potential roles in extracellular matrix remodeling in fibrosis. Thus, plasma proteome profiling can identify potential biomarkers and drug targets in liver disease.