Identification of immune microenvironment and PANoptosis-related biomarkers in diabetic kidney disease: PSMB8 and PSMB9

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease globally, but reliable diagnostic biomarkers are still lacking. Recent studies indicate that PANoptosis, a novel form of programmed cell death, is involved in DKD progression and may be influenced by the immune microenvironment. This study explores the relationship between PANoptosis and the immune microenvironment in DKD to discover new diagnostic biomarkers. Methods: Transcriptomic data from DKD-related datasets in the GEO database were integrated and batch-corrected as a training set. Differentially expressed genes (DEGs) were identified and intersected with PANoptosis-related genes, followed by functional enrichment analysis. Immune cell infiltration was assessed using CIBERSORT, and Weighted Gene Co-expression Network Analysis was applied to identify immune-related modules. Key genes overlapping with PANoptosis-related DEGs were selected as hub genes via LASSO regression and protein–protein interaction network analysis. Their diagnostic value was evaluated using ROC curves and clinical correlation analysis. GSEA was employed to elucidate the potential biological mechanisms of the hub genes in DKD. Finally, the expression of the hub genes was validated through cellular experiments, immunohistochemistry, and clinical samples. Results: The study identified PSMB8 and PSMB9 as hub genes. They demonstrated diagnostic accuracy in the validation set, with AUC values of 0.925 and 0.942, respectively. Hub gene expression was negatively correlated with glomerular filtration rate and positively correlated with serum creatinine. GSEA was enriched in inflammatory pathways. Moreover, hub genes were consistently upregulated in both high glucose- stimulated cellular experiments and DKD mouse model. Finally, PSMB8 expression exhibited a progressive increase from healthy controls to patients with type II diabetes mellitus and those with DKD. Conclusion: PSMB8 and PSMB9 are hub genes linked to immune microenvironment and PANoptosis in DKD, showing strong potential as diagnostic biomarkers.