PMID- 35187175
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220501
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2022
DP  - 2022
TI  - Identification of Potential Biomarkers of Type 2 Diabetes Mellitus-Related Immune 
      Infiltration Using Weighted Gene Coexpression Network Analysis.
PG  - 9920744
LID - 10.1155/2022/9920744 [doi]
LID - 9920744
AB  - 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.
CI  - Copyright (c) 2022 Ji Zhou et al.
FAU - Zhou, Ji
AU  - Zhou J
AUID- ORCID: 0000-0003-0394-0690
AD  - Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 
      266021, China.
FAU - Zhang, Xiaoyi
AU  - Zhang X
AD  - Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 
      266021, China.
FAU - Ji, Lixia
AU  - Ji L
AUID- ORCID: 0000-0001-6917-2597
AD  - Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 
      266021, China.
FAU - Jiang, Guohui
AU  - Jiang G
AUID- ORCID: 0000-0001-8607-6644
AD  - Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 
      266021, China.
LA  - eng
PT  - Journal Article
DEP - 20220209
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers)
RN  - 0 (Csf1r protein, mouse)
RN  - 0 (H2az2 protein, mouse)
RN  - 0 (Hcls1 protein, mouse)
RN  - 0 (Histones)
RN  - 0 (Receptors, Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics
MH  - Animals
MH  - Biomarkers
MH  - Databases, Genetic
MH  - Diabetes Mellitus, Type 2/*genetics/*immunology
MH  - Diet, High-Fat
MH  - *Gene Expression Profiling
MH  - *Gene Regulatory Networks
MH  - Histones/genetics
MH  - Mice
MH  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics
MH  - Toll-Like Receptor 9/genetics
PMC - PMC8849810
COIS- The authors have no competing interests to declare.
EDAT- 2022/02/22 06:00
MHDA- 2022/04/01 06:00
PMCR- 2022/02/09
CRDT- 2022/02/21 06:05
PHST- 2021/03/20 00:00 [received]
PHST- 2021/11/24 00:00 [revised]
PHST- 2021/12/23 00:00 [accepted]
PHST- 2022/02/21 06:05 [entrez]
PHST- 2022/02/22 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2022/02/09 00:00 [pmc-release]
AID - 10.1155/2022/9920744 [doi]
PST - epublish
SO  - Biomed Res Int. 2022 Feb 9;2022:9920744. doi: 10.1155/2022/9920744. eCollection 
      2022.