Significance of pyroptosis-related genes in the diagnosis and classification of diabetic kidney disease

Abstract

Objective This study aimed to identify the potential biomarkers associated with pyroptosis in diabetic kidney disease (DKD). Methods Three datasets from the Gene Expression Omnibus (GEO) were downloaded and merged into an integrated dataset. Differentially expressed genes (DEGs) were filtered and intersected with pyroptosis-related genes (PRGs). Pyroptosis-related DEGs (PRDEGs) were obtained and analyzed using functional enrichment analysis. Random forest, Least Absolute Shrinkage and Selection Operator, and logistic regression analyses were used to select the features of PRDEGs. These feature genes were used to build a diagnostic prediction model, identify the subtypes of the disease, and analyze their interactions with transcription factors (TFs)/miRNAs/drugs and small molecules. We conducted a comparative analysis of immune cell infiltration at different risk levels of pyroptosis. qRT-PCR was used to validate the expression of the feature genes. Results A total of 25 PRDEGs were obtained. These genes were coenriched in biological processes and pathways, such as the regulation of inflammatory responses. Five key genes (CASP1, CITED2, HTRA1, PTGS2, S100A12) were identified and verified using qRT-PCR. The diagnostic model based on key genes has a good diagnostic prediction ability. Five key genes interacted with TFs and miRNAs in 67 and 80 pairs, respectively, and interacted with 113 types of drugs or molecules. Immune infiltration of samples with different pyroptosis risk levels showed significant differences. Thus, CASP1, CITED2, HTRA1, PTGS2 and S100A12 are potential DKD biomarkers. Conclusion Genes that regulate pyroptosis can be used as predictors of DKD. Early diagnosis of DKD can aid in its effective treatment.