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Identification of key target genes and pathway analysis in nonalcoholic fatty liver disease via integrated bioinformatics analysis


 Background

This study aimed to explore the mechanisms underlying nonalcoholic fatty liver disease (NAFLD) and develop new diagnostic biomarkers for nonalcoholic steatohepatitis (NASH).
Methods

The microarray dataset GES83452 was downloaded from the NCBI-GEO database, and the differentially expressed RNAs (DERs) were screened between the NAFLD and non-NAFLD samples of the baseline and 1-year follow-up time point group based on the Limma package. Subsequently, the lncRNA–miRNA–mRNA regulation network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the regulated target genes in the ceRNA regulatory network were performed based on DAVID. Finally, PharmGKB database was used to search for the gene-related drug molecules, and the gene–drug connection network was constructed.
Results

A total of 561 DERs (268 downregulated and 293 upregulated) were screened in the baseline time point group, and 1163 DERs (522 downregulated and 641 upregulated) were screened in the 1-year follow-up time point group. A total of 74 lncRNA–miRNA pairs and 523 miRNA–mRNA pairs were obtained to construct lncRNA–miRNA–mRNA regulatory network. Subsequently, functional enrichment analysis revealed 28 GO and 9 KEGG pathways in the ceRNA regulatory network. LEPR and CXCL10 are involved in the Cytokine–cytokine receptor interaction (P = 1.86E-02), and the FOXO1 is involved in both the Insulin signaling pathway (P = 1.79E-02) and the pathways in cancer (P = 2.87E-02).
Conclusion

LEPR, CXCL10, and FOXO1 were the characteristic target genes for NAFLD.