Abstract
<jats:p>Differentiated thyroid cancer represents the most common malignancy of the endocrine system and is generally associated with a favorable long-term prognosis; however, a considerable subset of patients develops aggressive forms of the disease characterized by early local recurrence, regional lymph node involvement, distant metastases and partial or complete resistance to conventional therapeutic approaches, including surgery and radioactive iodine therapy. Despite advances in diagnostic imaging and treatment strategies, accurate prediction of disease behavior remains challenging. Currently used clinicopathological risk stratification models, based on tumor size, histological subtype and stage, do not fully reflect the underlying molecular and biological heterogeneity of thyroid tumors, which limits their prognostic accuracy and highlights the need for reliable molecular biomarkers capable of predicting disease progression, recurrence risk and treatment outcomes. MicroRNAs have emerged as key post-transcriptional regulators of gene expression involved in critical cellular processes such as proliferation, differentiation, apoptosis, angiogenesis and metastatic potential. Their dysregulation has been increasingly linked to carcinogenesis and tumor progression in various malignancies, including thyroid cancer. Altered microRNA expression profiles may influence tumor aggressiveness, invasion capacity and response to therapy, making them promising candidates for prognostic and biomarkers. The aim of this study was to identify selected microRNAs with potential prognostic significance in thyroid cancer and to assess their association with clinicopathological characteristics and patient survival. A comprehensive bioinformatic analysis was conducted using the UALCAN platform based on data derived from The Cancer Genome Atlas, evaluating the expression profiles of six microRNAs in thyroid cancer tissues compared with normal thyroid samples. Associations between microRNA expression levels and patient age, tumor stage, lymph node status, histological subtype and overall survival were statistically analyzed. In addition, a retrospective clinical analysis of 749 patients with thyroid pathology treated between 2019 and 2024 was performed in order to correlate molecular findings with real-world clinical outcomes and disease course. The results revealed significant overexpression of hsa-miR-15a-5p, hsa-miR-146b-5p, hsa-miR-221-5p and hsa-miR-222-3p in malignant thyroid tissues, whereas hsa-miR-199b-5p and hsa-miR-484 were markedly downregulated. Distinct expression patterns were closely associated with patient age, tumor stage, lymph node metastases and histological variants, suggesting their involvement in tumor progression and invasive behavior. Survival analysis demonstrated that increased expression of hsa-miR-199b-5p was associated with an approximately thirty-five percent reduction in five-year overall survival, indicating its substantial prognostic relevance. These findings support the critical role of microRNA dysregulation in thyroid carcinogenesis and disease progression and suggest that the identified microRNAs, particularly hsa-miR-199b-5p, may serve as valuable biomarkers for improved preoperative risk stratification, optimization of clinical decision-making and advancement of personalized therapeutic strategies in patients with differentiated thyroid cancer.</jats:p>