Th17 Cell-Related Gene Biomarkers in Autoimmune Thyroiditis: Comprehensive Bioinformatics Analysis and In Vivo Validation
Ziyu Liu, Ming Ren, Jiayun Li, Zhuo Zhao, Hao Gao, Guanghan Wang, Ying ZhangObjective:
The objective of this research was to comprehensively explore the molecular pathways through which Th17 cells contribute to autoimmune thyroiditis (AIT). This was achieved by pinpointing key gene biomarkers associated with Th17 cell activity and elucidating their regulatory functions in thyroid inflammation.
Methods:
High-throughput sequencing data of thyroid tissues from AIT patients and controls were obtained from the GEO database. The transcriptomic analysis was performed to quantify immune cell infiltration using ImmunCellAI, with a particular focus on Th17 cells. Candidate genes were identified through differential expression analysis between the groups, with criteria of |log2FC| > 1 and p.adj < 0.05. A protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape to identify hub genes. The core genes were validated in an independent dataset (GSE29315) and further tested in a NOD.H-2h4 mouse model. The diagnostic efficacy of the identified genes was assessed using ROC curve analysis.
Results:
In patients with autoimmune thyroiditis (AIT), the proportion of Th17 cells was significantly elevated, along with increased expression of genes associated with Th17 cells. Through transcriptomic analysis, a total of 235 upregulated and 128 downregulated differentially expressed genes (DEGs) were identified. Protein-protein interaction (PPI) network analysis highlighted 10 hub genes, including TLR2, TROAP, AURKB, and TK1, which were correlated with Th17 cell infiltration. These genes demonstrated high diagnostic accuracy, with area under the curve (AUC) values ranging from 0.85 to 1.00. Additionally, these genes were found to be upregulated in the thyroid tissues of AIT mouse models and correlated with inflammation and antibody levels.
Discussion:
This study identified Th17-related biomarkers (TLR2, TROAP, AURKB, TK1) in autoimmune thyroiditis (AIT), offering new molecular targets for targeted therapies. Future research is needed to elucidate cell-type-specific mechanisms underlying AIT pathogenesis using in vitro and in vivo models, thereby advancing personalized treatment strategies.
Conclusion:
Th17-related genes TLR2, TROAP, AURKB, and TK1 serve as high-performance diagnostic biomarkers for autoimmune thyroiditis and offer novel molecular targets for precision therapy.