Integrative analyzes of biomarkers and pathways for exploration the mechanisms and targets associated with pyroptosis in type 2 diabetes

Abstract

Abstract Purpose: This study aimed to investigate the association between pyroptosis and type 2 diabetes (T2D).Methods: Gene expression omnibus (GEO) was used to obtain two microarray datasets (GSE7014 and GSE25724), and differentially expressed genes (DEGs) were evaluated. DEGs in type 2 diabetes mellitus pyroptosis-related genes (T2DM-PRGs) were obtained by intersecting the differential genes associated with T2D and the genes associated with pyroptosis. The T2DM-PRGs were verified, and functional enrichment analysis was performed through gene ontology (GO) annotation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and gene set enrichment analysis (GSEA). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic predictive value of T2DM-PRG-related genes. The single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze immune infiltration in T2DM-PRGs and immune infiltration levels.Results：A total of 25 T2DM-PRGs were obtained. GSEA comprehensively proved that the majority of genes were enriched in the NF−kappa B signaling pathway and prostate cancer. The top five miRNAs targeting T2DM-PRG-related differentially expressed prognostic genes were PTEN, BRD4, HSP90AB1, VIM, and PKN2. The top five T2DM-PRG-related DEGs of transcription factors (TFs) were HSP90AB1, VIM, PLCG1, and PTEN. ROC analysis showed that in both datasets, PLCG1, PTEN, TP63, CHI3L1, SDHB, DPP8, BCL2, SERPINB1, ACE2, DRD2, DDX58, and BTK have good diagnostic performance. We found that T2DM-PRG-related genes in the GSE7014 dataset had 28 immune cells that were significantly different between T2DM tissues and normal tissues, whereas 28 immune cells in the GSE25724 dataset were substantially different between T2DM tissues and normal tissues.Conclusions：Exploration of pyroptosis-related mechanisms and biomarkers may contribute to the understanding of T2D pathophysiology and provide a novel therapeutic option for DM.