Abstract
Background Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade inflammation, showing an increasing trend. The infiltration of immune cells into adipose tissue has been shown to be an important pathogenic cause of T2DM. The purpose of this study is to use the relevant database to identify some abnormally expressed or dysfunctional genes related to diabetes from the perspective of immune infiltration. Methods Weighted gene coexpression network analysis (WGCNA) was employed to systematically identify the coexpressed gene modules and hub genes associated with T2DM development based on a microarray dataset (GSE23561) from the Gene Expression Omnibus (GEO) database. The key genes in modules highly related to clinical features were calculated and screened by using R software, and their participation in T2DM was determined by gene enrichment analysis. The mRNA levels of CSF1R, H2AFV, LCK, and TLR9 in pre-T2DM mice and normal wild-type mice were detected by WGCNA screening and real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results We constructed 14 coexpressed gene modules, and the brown module was shown to be significantly related to T2DM. Through verification of the protein-protein interaction (PPI) network, four upregulated hub genes, CSF1R, H2AFV, LCK, and TLR9, were screened from the brown module and successfully distinguishedT2DM patients from healthy people. These hub genes may be used as biomarkers and important indicators for patient diagnosis. Enrichment analysis showed that these hub genes were highly associated with IL-6-related inflammatory metabolism, immune regulation, and immune cell infiltration. Finally, we verified the hub genes CSF1R, LCK, and TLR9 in a T2DM animal model and found that their mRNA levels were significantly higher in animals with T2DM than in control group mice (NC). Conclusions In summary, our results suggest that these hub genes (CSF1R, LCK, and TLR9) can serve as biomarkers and immunotherapeutic targets for T2DM.
Highlights
Type 2 diabetes mellitus (T2DM) is an endocrine disease characterized by disorders of glucose, lipid, and protein metabolism [1]
The results showed that the mRNA levels of CSF1R, LCK, and Toll-like receptor 9 (TLR9) in the pre-T2DM group were higher than those in the control group (NC)
Because abnormal metabolism plays an important role in the progression of diabetes, we studied the expression levels of key genes associated with metabolism in diabetes and identified four hub genes closely related to the metabolic process (Figure 5(b))
Summary
Type 2 diabetes mellitus (T2DM) is an endocrine disease characterized by disorders of glucose, lipid, and protein metabolism [1]. The purpose of this study is to use the relevant database to identify some abnormally expressed or dysfunctional genes related to diabetes from the perspective of immune infiltration. Through verification of the protein-protein interaction (PPI) network, four upregulated hub genes, CSF1R, H2AFV, LCK, and TLR9, were screened from the brown module and successfully distinguishedT2DM patients from healthy people. These hub genes may be used as biomarkers and important indicators for patient diagnosis. Enrichment analysis showed that these hub genes were highly associated with IL-6-related inflammatory metabolism, immune regulation, and immune cell infiltration. Our results suggest that these hub genes (CSF1R, LCK, and TLR9) can serve as biomarkers and immunotherapeutic targets for T2DM
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
