Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). This study aimed to explore biomarkers, mechanisms, and potential novel agents regarding LN through bioinformatic analysis.

METHOD: Four expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were acquired. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses of DEGs were performed using the R software. The protein-protein interaction (PPI) network was developed using the STRING database. Additionally, five algorithms were used to screen out the hub genes. Expression of the hub genes were validated using Nephroseq v5. CIBERSORT was used to evaluate the infiltration of immune cells. Finally, The Drug-Gene Interaction Database was used to predict potential targeted drugs.

RESULT: FOS and IGF1 were identified as hub genes, with excellent specificity and sensitivity diagnosis of LN. FOS was also related to renal injury. LN patients had lower activated and resting dendritic cells (DCs) and higher M1 macrophages and activated NK cells than healthy control (HC). FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. The targeted drugs were dusigitumab and xentuzumab target for IGF1.

CONCLUSION: We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN.