Identification and functional characterization of hub genes CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets in thyroid cancer and Hashimoto’s thyroiditis

In this study, we sought to identify key molecular players in both thyroid cancer (TC) and Hashimoto's thyroiditis (HT) by analyzing differentially expressed genes (DEGs) and their potential as biomarkers. We utilized datasets from the Gene Expression Omnibus (GEO) database and identified CLTA, EDIL3, HAPLN1, and HIP1 as hub genes common to both TC and HT. These genes were significantly upregulated in TC cell lines compared to normal controls, with high diagnostic accuracy as indicated by Receiver Operating Characteristic (ROC) curve analysis. Further validation using the TCGA TC dataset revealed their significant upregulation in tumor tissues, particularly in advanced TC stages. Promoter methylation analysis indicated hypomethylation of these genes in TC, suggesting a role of methylation in their regulation. We also observed mutations and copy number variations (CNVs) in these hub genes, with CLTA and HIP1 showing significant amplifications, which may contribute to their overexpression in tumor samples. In addition, we conducted a meta-analysis to assess the impact of these genes on survival outcomes in TC patients, with results indicating that higher expression of HAPLN1 and HIP1 was associated with poor survival. Our study also highlighted the involvement of CLTA and EDIL3 in activating the Rap1 signaling pathway, crucial for cancer cell migration, proliferation, and invasion. These findings emphasize the potential of CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets for TC and HT.