Title of article :
Identification of a 17-gene-signature in Non-alcoholic Steatohepatitis and Its Relationship with Immune Cell Infiltration
Author/Authors :
Zhang, Junwang Gastroenterology Department - Second Hospital of Shanxi Medical University, Taiyuan City, China , Kang, Xumei Imaging Department - Second Hospital of Shanxi Medical University, Taiyuan City, China , Zhang, Ling Nursing Department - Second Hospital of Shanxi Medical University, Taiyuan City, China , Wang, Huiming Gastroenterology Department - Second Hospital of Shanxi Medical University, Taiyuan City, China , Deng, Zhihua Gastroenterology Department - Second Hospital of Shanxi Medical University, Taiyuan City, China
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 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 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.
Keywords :
Non-Alcoholic Steatohepatitis , Gene Expression Signatures , Immune Infiltration , Protein-Protein Interaction
Journal title :
Hepatitis Monthly