Novel ferroptosis gene biomarkers and immune infiltration profiles in diabetic kidney disease via bioinformatics

Abstract Diabetic kidney disease (DKD) is the primary cause of end‐stage renal disease, exhibiting high disability and mortality rates. Ferroptosis is vital for the progression of DKD, but the exact mechanism remains unclear. This study aimed to explore the potential mechanism of ferroptosis‐related genes in DKD and their relationship with the immune and to identify new diagnostic biomarkers to help treat and diagnose DKD. GSE30122 and GSE47185 were obtained from the Gene Expression Omnibus database and were integrated into a merged dataset, followed by functional enrichment analysis. Then potential differentially expressed genes were screened. Ferroptosis‐related differentially‐expressed genes were identified, followed by gene ontology analysis. Protein–protein interaction networks were constructed and hub genes were screened. The immune cell‐infiltrating state in the dataset was assessed using appropriate algorithms. Immune signature subtypes were constructed using the consensus clustering analysis. Hub gene expression was validated using qRT‐PCR and immunohistochemistry. A total of Eleven screened ferroptosis‐related differentially expressed genes were screened. Six potentially diagnostically favorable ferroptosis‐related hub genes were identified. Significantly increased expression of γδT cells, resting mast cells, and macrophages infiltration was observed in the DKD group. Additionally, two distinct immune signature subgroups were identified. Ferroptosis‐related hub genes were significantly correlated with differentially infiltrated immune cells. Six hub genes were significantly upregulated in HK‐2 cells following high glucose treatment and in human kidney tissues of patients with DKD. Six ferroptosis‐related hub genes were identified as potential biomarkers of diabetic kidney disease, but further validation is needed.