Journal of Inflammation Research (Feb 2023)

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes

  • Fu Y,
  • Xu L,
  • Zhang H,
  • Ding N,
  • Zhang J,
  • Ma S,
  • Yang A,
  • Hao Y,
  • Gao Y,
  • Jiang Y

Journal volume & issue
Vol. Volume 16
pp. 505 – 521

Abstract

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Yajuan Fu,1,2 Lingbo Xu,1– 3 Hui Zhang,1– 3 Ning Ding,1– 3 Juan Zhang,1– 3 Shengchao Ma,1– 3 Anning Yang,1– 3 Yinjv Hao,1– 3 Yujing Gao,1,2 Yideng Jiang1– 3 1National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 3School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Yujing Gao; Yideng Jiang, Email [email protected]; [email protected]: Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases.Methods: The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein–protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes.Results: We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases.We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies.Keywords: small molecular agents, immune infiltration, atherosclerosis, diabetes mellitus, inflammation

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