Journal Article

A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures

Hasoon, Megan, Daly, Ann K., Ekstedt, Mattias, Bugianesi, Elisabetta, Tiniakos, Dina, Ratziu, Vlad, Anstee, Quentin M., Boursier, Jerome, Alexander, Leigh, Govaere, Olivier, Cockell, Simon, Schattenberg, Jörn M.

2023

Overview

Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic signatures for active steatohepatitis and advanced fibrosis, and correlate these with hepatic transcriptomics to develop a proteo-transcriptomic signature of 31 markers. Deconvolution of this signature by single-cell RNA sequencing reveals the hepatic cell types likely to contribute to proteomic changes with disease progression. As an exemplar of use as a non-invasive diagnostic, logistic regression establishes a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM2), body mass index and type 2 diabetes mellitus status, to identify at-risk steatohepatitis. Govaere et al. integrate circulating protein data from more than 300 patients with non-alcoholic fatty liver disease (NAFLD) with transcriptomics and develop a non-invasive diagnostics tool to identify patients with at-risk NAFLD based on body mass index, type 2 diabetes status and four circulating proteins.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/39 / 631/443/319 / 692/4020/4021/1607/2750 / 692/53 / 82/79 / Adult / Aged / Biomarkers / Biomedical and Life Sciences / Biopsy / Body Mass Index / Cirrhosis / Cohort Studies / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Disease Progression / Fatty liver / Fatty Liver - complications / Fatty Liver - metabolism / Female / Fibrosis / Gene Expression Profiling / Humans / Immunohistochemistry / Inflammation / Letter / Life Sciences / Liver cirrhosis / Liver Cirrhosis - complications / Liver Cirrhosis - metabolism / Liver diseases / Logistic Models / Male / Metabolic syndrome / Metabolism / Middle Aged / Non-alcoholic Fatty Liver Disease - complications / Non-alcoholic Fatty Liver Disease - diagnosis / Non-alcoholic Fatty Liver Disease - genetics / Non-alcoholic Fatty Liver Disease - metabolism / Patients / Plasma / Proteins / Proteomics / Registries / Regression analysis / Single-Cell Gene Expression Analysis / Transcriptomics