Novel biomarkers related to oxidative stress and immunity in chronic kidney disease

Introduction: The incidence of chronic kidney disease (CKD) has been increasing in recent gradually becoming a global health crisis. Due to limited treatment options, novel molecular pathways are urgently required to advance the treatment and diagnosis of CKD. Materials and methods: The characteristics of differentially expressed genes (DEGs) in CKD patients were analyzed using Gene Expression Omnibus (GEO) database, and genes related to oxidative stress were retrieved from the Genecard database. Subsequently, a comprehensive approach applied, including immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and protein -protein interaction (PPI) network analysis, to identify hub genes among differentially expressed immune-related oxidative stress genes (DEIOSGs). Validation of genes was performed using an external data set, and diagnostic potential capability was evaluated through receiver operating curve (ROC) analysis. In animal experiments, the expression of genes in CKD was confirmed by inducing a CKD model through a 5/6 nephrectomy procedure. Finally, the relationship between these hub genes and clinical characteristics were assessed the Nephroseq v5 database. Results: 29 DEIOSGs were identified by comprehensive bioinformatics analysis. PPI analysis screened the hub genes NCF2, S100A9, and SELL. ROC analysis demonstrated excellent diagnostic efficacy. Further validation from other databases and animal experiments confirmed a substantial upregulation in the expression of hub genes in CKD. Additionally, clinical correlation analysis established a clear link between hub gene expression and renal function deterioration. Conclusions: Our study confirms NCF2, S100A9, and SELL as diagnostic biomarkers associated with immune response and oxidative stress in CKD, suggesting their potential as novel targets CKD diagnosis and treatment.