Bioinformatics Analysis of Gene Expression in Peripheral Blood Mononuclear Cells from Children with Type 1 Diabetes in 3 Periods

Abstract

Objective:

To explore the expression changes of potential key genes and relevant biological processes in peripheral blood mononuclear cells of children with newly diagnosis of type 1 diabetes (T1D).

Methods:

Microarray data GSE9006 were downloaded from Gene Expression Omnibus (GEO) database, including peripheral blood mononuclear cells samples from 43 children with newly diagnosed T1D (NEW), 19 one-month (1-MO) follow-up samples, 19 4-month (4-MO) follow-up samples and 24 healthy controls. The differentially expressed genes (DEGs) were identified using Affy package in R, and cluster analysis of DEGs were performed following functional enrichment analysis with Database for Annotation, Visualization and Integrated Discovery (DAVID) and construction of protein-protein interaction (PPI) network with STRING database.

Results:

We identified 73, 73, 96 DEGs in NEW group, 1-MO group and 4-MO group, respectively by comparing with healthy controls with |logFC|>0.58 and P-value<0.05. The cluster analysis of these DEGs showed that 4 genes, including human leukocyte antigen (HLA-DQA1), HLA-DRB4, integrin 3 (ITGB3) and killer cell lectin-like receptor subfamily F member 1 (KLRF1) were all significantly expressed in 3 groups, which were significantly enriched in asthma, T1D and intestinal immune network for IgA production pathway. And 57 genes enriched in cluster 5, which were only differentially expressed in NEW group, were involved in response to wounding, inflammatory response and blood coagulation as well as chemokine signaling pathway. Besides, the hub genes in PPI network of cluster 5 were identified, containing FOS, pro-platelet basic protein (PPBP), interleukin 8 (IL8), formyl peptide receptor-like 2 (FPR2) and platelet factor 4 (PF4).

Conclusion:

HLA-DQA1, HLA-DRB4, ITGB3 and KLRF1 might be targets for treatment of T1D, and 5 hub proteins, FOS, PPBP, IL8, FPR2 and PF4, were likely to be new markers for diagnosis of T1D.

Key words

children with type 1 diabetes - newly diagnosis - clusters - hub proteins

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