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A novel immune-related genes signature after bariatric surgery is histologically associated with non-alcoholic fatty liver disease.

ABSTRACT: Increasing evidence shows that immune-related genes (IRGs) play an important role in bariatric surgery (BS). We identified differentially expressed immune-related genes (DEIRGs) of adipose tissue after BS by analysing the two expression profiles of GEO (GSE59034 and GSE29409). Subsequently, enrichment analysis, GSEA and PPI networks were examined to identify the hub IRGs and related pathways. The performance of the signature was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC). CIBERSORT algorithm was used to evaluate the relative abundance of infiltrated immune cells.42 DEIRGs were found between the GSE59034 and GSE29409 datasets. The AUC of the signature was 0.904 and 0.865 in the GSE58979 and GSE48452, respectively. Interestingly, the signature also showed good performance in diagnosing non-alcoholic fatty liver disease (NAFLD) (AUC was 0.834 and 0.800, respectively). The number of neutrophils, macrophages M2, macrophages M0 and dendritic cells activated decreased significantly. After BS, the infiltration of T cells regulatory, monocytes, mast cells resting and plasma cells in adipose tissue increased. The novel proposed IRGs signature reveals the underlying immune mechanism of BS and is a promising biomarker for distinguishing the severity of NAFLD. This will provide new insights into strategies for treating obesity and NAFLD.

SUBMITTER: Song Y

PROVIDER: S-EPMC8437528 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe morbidity and mortality rates of patients with non-alcoholic fatty liver disease (NAFLD) have been steadily increasing in recent years. Previous studies have confirmed the important role of ferroptosis in NAFLD development; however, the precise mechanism through which ferroptosis influences NAFLD occurrence remains unclear. The present study aimed to identify and validate ferroptosis-related genes involved in NAFLD pathogenesis and to investigate the underlying molecular mechanisms of NAFLD.MethodsWe downloaded microarray datasets GSE72756 and GSE24807 to identify differentially expressed genes (DEGs) between samples from healthy individuals and patients with NAFLD. From these DEGs, we extracted ferroptosis-related DEGs. GSE89632, another microarray dataset, was used to validate the expression of ferroptosis-related genes. A protein-protein interaction (PPI) network of ferroptosis-related genes was then constructed. The target genes were also subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, competing endogenous RNA networks were constructed. We used the CIBERSORT package to evaluate the infiltration of immune cells infiltration in NAFLD.ResultsFive ferroptosis-related genes (SCP2, MUC1, DPP4, SLC1A4, and TF) were identified as promising diagnostic biomarkers for NAFLD. Enrichment analyses revealed that these genes are mainly involved in metabolic processes. NEAT1-miR-1224-5p-SCP2, NEAT1-miR-485-5p-MUC1, MALAT1-miR-485-5p-MUC1, and CNOT6-miR-145-5p-SLC1A4 are likely to be the potential RNA regulatory pathways that affect NAFLD development. Principal component analysis indicated significant differences in immune cell infiltration between the two groups.ConclusionsThis study identified five ferroptosis-related genes as potential biomarkers for diagnosing NAFLD. The correlations between the expression of ferroptosis-related genes and immune cell infiltration might shed light on the study of the molecular mechanism underlying NAFLD development.

Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Autophagy plays a vital role in NAFLD development and progression. We aimed to establish a novel autophagy-related gene (ARG) signature as a therapeutic target in NAFLD patients based on high-throughput sequencing data.MethodsARGs obtained from the HAMdb and high-sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed ARGs (DEARGs) between normal and NASH tissues. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore potential biological and pathological functions of DEARGs. The protein-protein interaction (PPI) network of the DEARGs was established through the STRING website, and visualized by Cytoscape. In addition, hub genes were validated by an independent dataset GSE89632. Finally, we performed Gene Set Variation Analysis (GSVA) pathway-related analysis to identify the pivotal signaling pathways and genes for the progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH).ResultsA total of 76 DEARGs were identified in the GSE126848 dataset, of which 45 genes were upregulated and 31 genes were downregulated. GO analysis showed that the biological functions of DEARGs focused primarily on autophagy, cellular response to external stimulus, fibroblast proliferation, late endosome, and ubiquitin protein ligase binding. KEGG pathway analysis showed that these DEARGs were mainly involved in the apoptosis, PI3K-Akt signaling pathway, and estrogen signaling pathway. Among DEGs, 9 most closely related genes were identified from the PPI network. Furthermore, NOS3, IGF1, VAMP8, FOS, and HMOX1 were verified in the GSE89632 dataset. At last, the MAPK signal pathway was identified as important pathway, and JUN was identified as a key gene involved in the progression from NAFL to NASH.ConclusionThis study may provide credible molecular biomarkers in terms of screening and diagnosis for NAFLD. Meanwhile, it also serves as a basis for exploring the molecular mechanisms underlying the progression of NAFL to NASH.

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A novel immune-related genes signature after bariatric surgery is histologically associated with non-alcoholic fatty liver disease.

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