Related Experiment Video
Updated: Aug 30, 2025
Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated
Yueyue Wang1, Yanfei Shao2,3, Haitao Zhang1
1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Background:
Thyroid-associated ophthalmopathy (TAO) is a common and organ-specific autoimmune disease. Early diagnosis and novel treatments are essential to improve the prognosis of TAO patients. Therefore, the current work was performed to identify the key genes and pathways for the biological and clinical implications of TAO through comprehensive bioinformatics analysis and a series of clinical validations.
Methods:
GSE105149 and GSE185952 were obtained from the Gene Expression Omnibus (GEO) database for analysis. The data were normalized to identify the common differentially expressed genes (DEGs) between the two datasets, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to assess key pathways in TAO. Protein-protein interaction (PPI) networks and hub genes among the common DEGs were identified. Furthermore, we collected the general information and blood samples from 50 TAO patients and 20 healthy controls (HCs), and the expression levels of the proteins encoded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship between the ELISA data and the TAO development.
Results:
Several common pathways, including neuroactive ligand-receptor interaction, the IL-17 signaling pathway, and the TNF signaling pathway, were identified in both datasets. In parallel, 52 common DEGs were identified. The KEGG analysis showed that these common DEGs are mainly enriched in long-term depression, the VEGF signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, and cytokine-cytokine receptor interactions. The key hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R were screened out through the PPI network. As confirmation, the ELISA results indicated that protein expression levels of PRKCG, OSM, CSF3R, and DPP4 were significantly upregulated in TAO patients compared with HCs. In addition, PRKCG and DPP4 were verified to show value in diagnosing TAO, and CSF3R was found to be a valuable diagnostic marker in distinguishing active TAO from inactive TAO.
Conclusions:
Inflammation- and neuromodulation-related pathways might be closely associated with TAO. Based on the clinical verification, OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as inflammation- or neuromodulation-related biomarkers for TAO, providing novel insights for the diagnosis and treatment of TAO.
Insights
This study identifies key genes and pathways in Thyroid-Associated Ophthalmopathy (TAO) using bioinformatics and clinical validation. PRKCG, DPP4, and CSF3R show potential as diagnostic biomarkers for TAO.
Area of Science:
- Immunology
- Genomics
- Ophthalmology
Background:
- Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease requiring early diagnosis and novel treatments.
- Identifying key genes and pathways is crucial for understanding TAO's biological and clinical implications.
Purpose of the Study:
- To identify key genes and pathways associated with TAO through comprehensive bioinformatics analysis.
- To clinically validate potential biomarkers for TAO diagnosis and progression.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets (GSE105149, GSE185952) to identify common differentially expressed genes (DEGs).
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to assess key pathways.
- Constructed protein-protein interaction (PPI) networks to identify hub genes.
- Validated protein expression of hub genes in serum samples from TAO patients and healthy controls (HCs) using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Identified common pathways including neuroactive ligand-receptor interaction, IL-17, and TNF signaling.
- Discovered 52 common DEGs, enriched in pathways like VEGF signaling and cytokine-cytokine receptor interactions.
- Screened hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R.
- ELISA confirmed upregulated PRKCG, OSM, CSF3R, and DPP4 in TAO patients.
- PRKCG and DPP4 demonstrated diagnostic value for TAO; CSF3R distinguished active from inactive TAO.
Conclusions:
- Inflammation- and neuromodulation-related pathways are strongly associated with TAO.
- OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as novel biomarkers for TAO diagnosis and treatment.
- Findings offer new insights into the diagnosis and management of TAO.
Related Concept Videos
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
01:23The Thyroid Gland
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...