Identification of Key Genes and Immune Infiltrate in Nonalcoholic fatty liver disease: A Bioinformatic Analysis

Objective Nonalcoholic fatty liver disease (NAFLD) has become the most importantgenes are involved in the pathogenesis of NAFLD.cause of chronic liver disease. To analyze the differentially expressed genes and immune infiltration between NAFLD and normal liver tissue based on Gene Expression Omnibus (GEO), and to explore the related molecular mechanisms.Methods Data GSE89632 was downloaded from GEO database, including 63 samples, including 39 cases of NAFL (including 20 cases of simple fatty liver, 19 cases of nonalcoholic steatohepatitis) and 24 cases of healthy control. The “limma” package in R was used to process the data and to screen differentially expressed genes. The DAVID database was applied to perform the enrichment analysis of Gene Ontology (GO) terms and KEGG pathways on the top 375 differentially expressed genes.The protein-protein interaction (PPI) network was constructed using the STRING database, and Cytoscape software program (Version 3.9. 1) was used to visualize the PPI network and identify key genes. The "CIBERSORT" package was used to detect immune infiltration in NAFLD.Results A total of 375 differentially expressed genes were screened, including 126 up-regulated genes and 249 down-regulated genes. GO analysis showed that the biological processes were mainly enriched in Inflammatory response regulation, macrophage activation, leukocyte adhesion regulation, myeloid leukocyte activation, positive regulation of response to external stimuli . KEGG enrichment analysis showed that the signaling pathways of differentially expressed genes were mainly associated with TNF 、 IL- 17 、 transcriptional misregulation in cancer, AGE-RAGE signaling pathway in diabetes complications, cytokine-cytokine receptor interaction and JAK-STAT signaling pathways. The top four hub genes were IL-6, MYC, IL- 1β, JUN. Immunoinfiltration analysis showed significant differences between neutrophils, activated dendritic cells, mast cells, M2 macrophages, monocytes, γ δ T cells, and initial B cells (r< 0.01), revealing the types of immune cells associated with NAFLD pathogenesis. Further analysis showed that the changes of immune microenvironment were correlated with the identified hub genes.Conclusions Multiple immune cells and identified key