Identification of a 17-gene-signature in Non-alcoholic Steatohepatitis and Its Relationship with Immune Cell Infiltration

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma, but the understanding of the regulatory mechanisms driving NASH is not comprehensive. Objectives: We aimed to identify the potential markers of NASH and explore their relationship with immune cell populations. Methods: Five gene expression datasets for NASH were downloaded from the Gene Expression Omnibus and European Bioinformatics Institute (EBI) Array Express databases. Differentially expressed genes (DEGs) between NASH and controls were screened. Gene Ontology-Biological Process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for functional enrichment analysis of DEGs. Among the candidate genes selected from the protein-protein interaction (PPI) network and module analysis, DEG signatures were further identified using least absolute shrinkage and selection operator (LASSO) regression analysis. The Spearman correlation coefficient was calculated to assess the correlation between DEG signatures and immune cell abundance based on the CIBERSORT algorithm. Results: We screened 403 upregulated, and 158 downregulated DEGs for NASH, and they were mainly enriched in GO-BP, including the inflammatory response, innate immune response, signal transduction, and KEGG pathways, such as the pathways involved in cancer (e.g., the PI3K-Akt signaling pathway), and focal adhesion. We then screened 73 candidate genes from the PPI network and module analysis and finally identified 17 DEG signatures. By evaluating their relationship with immune cell populations, 12 DEG signatures were found to correlate with activated dendritic cells, resting dendritic cells, M2 macrophages, monocytes, neutrophils, and resting memory CD4 T cells, which were significantly different between the NASH and control tissues. Conclusions: We identified a 17-DEG-signature as a candidate biomarker for NASH and analyzed its relationship with immune infiltration in NASH.