Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database.

BACKGROUND: We performed a differential analysis, enrichment analysis, and immune-infiltration analysis of the thyroid-associated ophthalmopathy (TAO) gene using data from the Gene Expression Omnibus (GEO) database to provide a theoretical basis for understanding the immune-related mechanisms of TAO.

METHODS: We searched the GEO database for "Graves disease" and selected the genes expressed in the lacrimal gland of thyroid-related eye disease patients as the test group and the genes expressed in the lacrimal gland of normal subjects as the control group. Immune-related differentially expressed genes (irDEGs), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction, gene-gene interaction (GGI) network, pivotal gene identification, and immune-infiltration analyses were carried out, and finally, risk-prediction models were constructed.

RESULTS: The GSE105149 and GSE58331 data sets contained 200 DEGs, of which 15 were immune-related. In relation to the GO biological processes (BPs), the main pathways included the interleukin (IL)-27-mediated signaling pathway, the IL-35-mediated signaling pathway, cytokine activity, T helper 17 cell differentiation, the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, cytokine-cytokine receptor interaction, the Janus kinase and signal transducer and activator of transcription signaling pathway, and other KEGG pathways. Cluster of differentiation (CD)4+ T cells, monocytes, M0 macrophages, and Mast cells were significantly elevated in TAO, while M2 macrophages were significantly reduced. In the immune cell correlation analysis, CD4+ T cells and naïve B cells were significantly positively correlated with activated natural killer (NK) cells, and Mast cells were positively correlated with plasma cells and negatively correlated with M2 macrophages. Risk models for a total of 6 genes (i.e., Janus kinase 1, heat shock protein 90-α, phospholipase A 2 group IIA, fibroblast growth factor 3, glucose-6-phosphate isomerase, and protein disulfide isomerase family A, member 2), were constructed, and over 100 potential targeted therapeutic agents were obtained.

CONCLUSIONS: In TAO, various types of immune cells infiltrate to different degrees, and the immune response and inflammatory response are throughout the disease. Our constructed risk-prediction models provide a reference for predicting TAO.