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BIOINFORMATIC ANALYSIS IDENTIFIES POTENTIALLY KEY DIFFERENTIALLY EXPRESSED GENES AND PATHWAYS IN ORBITAL ADIPOSE TISSUES OF PATIENTS WITH THYROID EYE DISEASE.

CONTEXT: Thyroid eye disease (TED), an orbital inflammatory status, generally occurred in Graves' disease.

OBJECTIVE: This study aimed to acquire further insight into molecular mechanisms of TED, especially several key involved genes and pathways.

DESIGN: The microarray dataset GSE58331 including expression data for orbital adipose tissue samples, isolated from TED patients and normal controls, was downloaded from a publicly accessible Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified from 23 adipose tissues of TED patients versus 20 samples from normal controls.

SUBJECTS AND METHODS: A protein-protein interaction network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes and Cytoscape 3.6.0. Several hub genes/proteins were extracted from the protein-protein interaction network based on connectivity degree. Furthermore, we used the iRegulon plugin of Cytoscape3.6.0 to predict the transcription factors (TFs).

RESULTS: A total of 678 DEGs (538 up- and 140 down-regulated genes) were identified in TED patients. Proopiomelanocortin (POMC), interleukin 2 (IL-2), G protein subunit gamma 3 (GNG3), CXC motif chemokine receptor 4 (CXCR4), toll like receptor 4 (TLR4), colony stimulating factor 1 receptor (CSF1R), lysophosphatidic acid receptor 3 (LPAR3), CXC motif chemokine ligand-8 (CXCL8), etc., were considered as the hub genes among the DEGs. There were 6 TFs predicted to be differentially expressed in regulating the DEGs related to TED. A total of 71 DEGs had been reported to be associated with TED in the Comparative Toxicogenomics Database.

CONCLUSIONS: Through this analysis, we have identified plenty of potential biomarkers and pathways which may have an important role in the pathogenesis of TED. However, these findings require verification by more detailed future experimental studies.

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