Hub genes and key pathways of Graves' disease: bioinformatics analysis and validation

This study aims to identify hub genes associated with the onset and progression of Graves' disease (GD) with the goal of developing novel biomarkers to enhance diagnosis and improve patient outcomes.

mRNA profiles from thyroid tissue samples (24 GD vs. 24 normal controls) were obtained from GEO (GSE9340), ArrayExpress (E-MEXP-2612), and GTEx (Thyroid dataset). After batch correction via SVA algorithm, 366 differentially expressed genes (DEGs) were identified using limma. Functional enrichment, protein-protein interaction networks, and immune microenvironment analysis were performed. Hub genes were validated in clinical thyroid specimens (3 GD vs. 3 controls) using RT-qPCR.

A total of 366 DEGs were identified in the diseased and normal groups. Among these, eight hub genes (TYROBP, CSF1R, CD163, ITGAM, CD86, FCGR3B, ITGB2, and IL10RA) showed strong correlations with immune cell content. These genes were predominantly enriched in pathways related to amino acid metabolism, viral protein interactions with cytokines and cytokine receptors, phagosome, chemokine signaling, programmed cell death, NF-κB, and other pathways. Additionally, these hub genes were linked to 39 regulatory factors. mRNA levels of these hub genes were validated in clinical samples through RT-qPCR. It is noteworthy that eight genes were found to be upregulated in GD samples.

The study highlights the potential impact of ITGB 2, TYROBP, CSF1R, CD163, ITGAM, CD86, FCGR3B, and IL10RA on the development and progression of GD, supporting their role as potential biomarkers.