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Original Article
- Type 1 Diabetes
- Identification of Key Genes and Pathways in Peripheral Blood Mononuclear Cells of Type 1 Diabetes Mellitus by Integrated Bioinformatics Analysis
- Xing Li, Mingyu Liao, Jiangheng Guan, Ling Zhou, Rufei Shen, Min Long, Jiaqing Shao
- Diabetes Metab J. 2022;46(3):451-463. Published online April 1, 2022
- DOI: https://doi.org/10.4093/dmj.2021.0018
- 7,021 View
- 292 Download
- 6 Web of Science
- 9 Crossref
-
Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM.
Methods
Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb).
Results
We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM.
Conclusion
These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications. -
Citations
Citations to this article as recorded by
- Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer
Zhihao Zhao, Qilin Wang, Fang Zhao, Junnan Ma, Xue Sui, Hyok Chol Choe, Peng Chen, Xue Gao, Lin Zhang
BMC Genomics.2024;[Epub] CrossRef - Bioinformatics analysis identifies TGF-β signaling pathway-associated molecular subtypes and gene signature in diabetic foot
Guanggang Du, Jie Chen, Xuezhu Zhu, Zongdong Zhu
iScience.2024; 27(3): 109094. CrossRef - Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID-19 Using Bioinformatics Approaches
Shudeb Babu Sen Omit, Salma Akhter, Humayan Kabir Rana, A. R. M. Mahamudul Hasan Rana, Nitun Kumar Podder, Mahmudul Islam Rakib, Ashadun Nobi, Ali Imran
BioMed Research International.2023; 2023: 1. CrossRef - Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus
Mingshu Huang, Weixing Chen, Min Wang, Yisheng Huang, Hongyu Liu, Yue Ming, Yuanxin Chen, Zhengming Tang, Bo Jia
BioDrugs.2023; 37(3): 331. CrossRef - Identification of the key genes of tuberculosis and construction of a diagnostic model via weighted gene co-expression network analysis
Baiying Li, Lifang Sun, Yaping Sun, Libo Zhen, Qi Qi, Ting Mo, Huijie Wang, Meihua Qiu, Qingshan Cai
Journal of Infection and Chemotherapy.2023; 29(11): 1046. CrossRef - Probing biological network in concurrent carcinomas and Type-2 diabetes for potential biomarker screening: An advanced computational paradigm
Abdullah Al Marzan, Shatila Shahi, Md Sakil Arman, Md Zafrul Hasan, Ajit Ghosh
Advances in Biomarker Sciences and Technology.2023; 5: 89. CrossRef - Transcriptional analysis of human peripheral blood mononuclear cells stimulated by Mycobacterium tuberculosis antigen
Jing Wei, Fangzheng Guo, Yamin Song, Kun Xu, Feiyang Lin, Kangsheng Li, Baiqing Li, Zhongqing Qian, Xiaojing Wang, Hongtao Wang, Tao Xu
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef - Combining bioinformatics and machine learning algorithms to identify and analyze shared biomarkers and pathways in COVID-19 convalescence and diabetes mellitus
Jinru Shen, Yaolou Wang, Xijin Deng, Si Ri Gu Leng Sana
Frontiers in Endocrinology.2023;[Epub] CrossRef - Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus
Zhaoxiang Wang, Li Zhang, Fengyan Tang, Zhongming Yang, Mengzhu Wang, Jue Jia, Dong Wang, Ling Yang, Shao Zhong, Guoyue Yuan
Endocrine.2022; 78(2): 270. CrossRef
- Single-cell and transcriptomic analyses reveal the influence of diabetes on ovarian cancer
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