Human hepatic gene expression signature of non-alcoholic fatty liver disease progression, a meta-analysis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a wide-spread chronic liver condition that places patients at risk of developing cardiovascular diseases and may progress to cirrhosis or hepatocellular carcinoma if untreated. Challenges in clinical and basic research are caused by poor understanding of NAFLD mechanisms. The purpose of current study is to describe molecular changes occurring in human liver during NAFLD progression by defining a reproducible gene expression signature. We conduct a systematic meta-analysis of published human gene expression studies on liver biopsies and bariatric surgery samples of NAFLD patients. We relate gene expression levels with histology scores using regression models and identify a set of genes showing consistent-sign associations with NAFLD progression that are replicated in at least three independent studies. The analysis reveals genes that have not been previously characterized in the context of NAFLD such as HORMAD2 and LINC01554. In addition, we highlight biomarker opportunities for risk stratification and known drugs that could be used as tool compounds to study NAFLD in model systems. We identify gaps in current knowledge of molecular mechanisms of NAFLD progression and discuss ways to address them. Finally, we provide an extensive data supplement containing meta-analysis results in a computer-readable format.

hnRNPU/TrkB Defines a Chromatin Accessibility Checkpoint for Liver Injury and Nonalcoholic Steatohepatitis Pathogenesis

“…The liver transcriptome is highly responsive to nutritional, hormonal, and circadian cues. Reprogramming of the liver transcriptome as a consequence of altered epigenetic state and chromatin accessibility in hepatocytes is a fundamental feature of NAFLD . Despite this, the molecular nature of the regulatory network that governs chromatin architecture in the liver remains obscure.…”

“…Reprogramming of the liver transcriptome as a consequence of altered epigenetic state and chromatin accessibility in hepatocytes is a fundamental feature of NAFLD. (14,40,41) Despite this, the molecular nature of the regulatory network that governs chromatin architecture in the liver remains obscure. In this study, we uncovered hnRNPU as a regulator of chromatin accessibility across the genome that functions to protect hepatocytes from stress-induced cell injury (Fig.…”

Hepatic expression profiling identifies steatosis-independent and steatosis-driven advanced fibrosis genes

“…Transcriptional factor motif enrichment analysis was performed on the ELF score-correlated gene set using the RcisTarget package in R (32). For meta-analysis, lists of DEGs were taken from published data sets (33)(34)(35)98). The Vennerable package (https://github.com/js229/Vennerable, commit 46057c9) was used to create the Venn diagram comparing all the data sets.…”

Gene expression profiling of The Cancer Genome Atlas supports an inverse association between body mass index (BMI) and major oesophageal tumour subtypes

“…A general rule of thumb is that one requires about 30 samples to assume a normal distribution. A sample size of 30 would result in a Spearman correlation ( rho ) cutoff of 0.36, with rho decreasing as sample size increases (see [12]). In our analysis we employed a blanket rho cutoff of 0.30 and retained genes with a false-discovery-corrected P -value less than 0.01 (Bonferroni-corrected to account for a total of 60,483 genes tested).…”