CD8+ T and NK cells characterized by upregulation of NPEPPS and ABHD17A are associated with the co-occurrence of type 2 diabetes and coronary artery disease.

Abstract

Coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) are closely related. The function of immunocytes in the pathogenesis of CAD and T2DM has not been extensively studied. The quantitative bioinformatics analysis of the public RNA sequencing database was applied to study the key genes that mediate both CAD and T2DM. The biological characteristics of associated key genes and mechanism of CD8+ T and NK cells in CAD and T2DM are our research focus. With expression profiles of GSE66360 and GSE78721 from the Gene Expression Omnibus (GEO) database, we identified core modules associated with gene co-expression relationships and up-regulated genes in CAD and T2DM using Weighted Gene Co-expression Network Analysis (WGCNA) and the 'limma' software package. The enriched pathways of the candidate hub genes were then explored using GO, KEGG and GSEA in conjunction with the immune gene set (from the MSigDB database). A diagnostic model was constructed using logistic regression analysis composed of candidate hub genes in CAD and T2DM. Univariate Cox regression analysis revealed hazard ratios (HRs), 95% confidence intervals (CIs), and p-values for candidate hub genes in diagnostic model, while CIBERSORT and immune infiltration were used to assess the immune microenvironment. Finally, monocytes from peripheral blood samples and their immune cell ratios were analyzed by flow cytometry to validate our findings. Sixteen candidate hub genes were identified as being correlated with immune infiltration. Univariate Cox regression analysis revealed that NPEPPS and ABHD17A were highly correlated with the diagnosis of CAD and T2DM. The results indicate that CD8+ T cells (p = 0.04) and NKbright cells (p = 3.7e-3) are significantly higher in healthy controls than in individuals with CAD or CAD combined with T2DM. The bioinformatics results on immune infiltration were well validated by flow cytometry. A series of bioinformatics studies have shown ABHD17A and NPEPPS as key genes for the co-occurrence of CAD and T2DM. Our study highlights the important effect of CD8+ T and NK cells in the pathogenesis of both diseases, indicating that they may serve as viable targets for diagnosis and therapeutic intervention.