Identification of Key Genes for Alcoholic Hepatitis Using Integrated Network Analysis of Differential lncRNA and Gene Expression

利用差异表达lncRNA和基因表达的整合网络分析鉴定酒精性肝炎的关键基因

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Abstract

Alcoholic liver disease (ALD) is a type of liver disease with complex pathogenic factors. In 2019, alcohol caused 11 million life-years to be lost globally, and the mortality rate has continued to rise. This study aims to explore the exclusive gene profile of AH and construct an mRNA-lncRNA regulatory network through an integrative analysis and database validation to reveal potential key biomarkers. We obtained expression data for alcoholic hepatitis from the GEO database; screened differentially expressed genes (DEGs) through a weighted gene co-expression network analysis (WGCNA); conducted a GO&KEGG analysis; and focused on the enrichment pathways for the top 20 genes. Hub genes were selected using cytoHubba and MCODE to construct the mRNA-lncRNA regulatory network, and key genes were confirmed using GSE167308 and GSE28619. We obtained 2552 differentially expressed mRNAs and 555 differentially expressed lncRNAs from three databases. Differentially expressed genes are mainly involved in pathways such as lipid metabolism disorders, complement activation, the activation of cancer-related pathways, the excessive activation of inflammatory immunity, and the initiation of cell adhesion and fibrosis. Based on the hub gene analysis, we screened out 43 key genes. By constructing the key mRNA-lncRNA-pathway network, we identified 12 mRNAs (AQP1, ELOVL7, ITPR3, KRT19, KRT23, LAMC2, MMP7, PROM1, SPINT1, STK39, TNFRSF21, and VTCN1) and 14 lncRNAs that play an important role in the occurrence and development of alcoholic hepatitis. To sum up, this article mainly expounds upon the key genes in the occurrence and development of alcoholic hepatitis. The key genes are mainly concentrated within signaling pathways such as metabolic pathways, fatty acid metabolism, and cancer pathways. Twelve differentially expressed mRNAs in the co-expression network can be used as biomarkers and intervention targets for the diagnosis and treatment of alcoholic hepatitis.

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