Identification of Key Biomarkers and Immune Infiltration in Liver Tissue after Bariatric Surgery.

BACKGROUND

Few drugs are clearly available for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH); nevertheless, mounting studies have provided sufficient evidence that bariatric surgery is efficient for multiple metabolic diseases, including NAFLD and NASH, while the molecular mechanisms are still poorly understood.

METHODS

The mRNA expression profiling of GSE48452 and GSE83452 were retrieved and obtained from the Gene Expression Omnibus (GEO) database. The limma package was employed for identifying differentially expressed genes (DEGs), followed by clusterProfiler for performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and GSEA software for performing GSEA analyses. The PPI network analyses were constructed using Metascape online analyses. WGCNA was also utilized to identify and verify the hub genes. CIBERSORT tools contributed to the analysis of immune cell infiltration of liver diseases.

RESULTS

We identify coexpressed differential genes including 10 upregulated and 55 downregulated genes in liver tissue after bariatric surgery. GO and KEGG enrichment analyses indicated that DEGs were remarkably involved in the immune response. GSEA demonstrated that DEGs were markedly enriched in the immune response before surgery, while most were enriched in metabolism after surgery. Seven genes were screened through the MCC algorithm and KME values, including SRGN, CD53, EVI2B, MPEG1, NCKAP1L, LCP1, and TYROBP. The mRNA levels of these genes were verified in the Attie Lab Diabetes Database, and only LCP1 was found to have significant differences and correlation with certain immune cells.

CONCLUSION

Our knowledge of the mechanisms by which bariatric surgery benefits the liver and the discovery of LCP1 is expected to serve as potential biomarkers or therapeutic targets for NAFLD and NASH.