Identification and assessment of FN1, MET, KRT19 and CLDN1 as key dysregulated genes in papillary thyroid cancer through transcriptomic profiling and expression analysis.

Abstract

Papillary thyroid carcinoma (PTC) is the most common type of endocrine malignancy worldwide. Although the prognosis of PTC is generally favorable, understanding its molecular mechanisms is of great importance for improving diagnostic stratification and clinical management. The present study aimed to identify genes that are consistently differentially expressed in PTC through an integrative analysis of transcriptomic datasets combined with experimental validation. Differential expression analysis of six RNA-sequencing datasets comparing PTC and adjacent non-tumor tissue identified 131 commonly dysregulated genes, including 128 upregulated and 3 downregulated genes. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the aforementioned differentially expressed genes were significantly associated with 'tissue development', 'cell adhesion' and 'plasma membrane organization'. Additionally, protein-protein interaction network and centrality analyses identified fibronectin 1 (FN1), MET proto-oncogene, receptor tyrosine kinase (MET), keratin 19 (KRT19) and claudin 1 (CLDN1) as hub genes consistently ranked among the top candidates. The mRNA expression levels of these genes were detected in an independent cohort of 86 patients, including 42 with PTC and 44 with a benign thyroid nodule (BTN), by reverse transcription-quantitative PCR. Furthermore, in silico analysis was performed using data from the Human Protein Atlas. The results demonstrated that all 4 genes were significantly upregulated in PTC tissues compared with those in BTN tissues (P<0.001). Collectively, these findings support the presence of a reproducible transcriptomic pattern in PTC. Furthermore, FN1, MET, KRT19 and CLDN1 were identified as robust candidate biomarkers that warrant further functional characterization and clinical evaluation.