Biomarkers associated with papillary thyroid carcinoma and Hashimoto's thyroiditis: Bioinformatic analysis and experimental validation

Abstract

Purpose: Hashimoto's thyroiditis (HT) is widely recognized as a risk factor for papillary thyroid carcinoma (PTC). This study aimed to identify key targets involved in the progression of HT to PTC.

Methods: Microarray datasets (GSE138198) for PTC, HT, and PTC with HT in the background (PTC-W) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and analyzed between normal and diseased groups. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) network analysis was conducted to identify hub genes, which were validated through qPCR and immunohistochemical (IHC) analysis. ROC analysis was then carried out based on the expression levels of hub genes in clinical plasma samples.

Results: A total of 78 shared DEGs were identified from the GEO dataset. GO and KEGG analyses highlighted pathways such as epithelial-to-mesenchymal transition (EMT) and PI3K-Akt signaling. The analysis of immune cell subtypes showed that the hub genes were commonly associated with various immune cells, particularly dendritic cells (DC) and macrophages. Ten hub genes-LYZ, FCER1G, CCL18, CXCL9, ALOX5, TYROBP, C1QB, CTSS, MET, and FAM20A-were identified from the PPI network. qPCR and IHC confirmed the overexpression of MET and FAM20A in PTC-W. The area under the curve (AUC) of the ROC analysis was 0.889 for MET and 0.825 for FAM20A.

Conclusion: This study identified two hub genes, MET and FAM20A, with potential diagnostic value in HT and PTC.

Keywords: Bioinformatics; Biomarker; Disease association; Hashimoto’s thyroiditis; Immune infiltration; Papillary thyroid carcinoma.