Investigation of the Genetic Background of Papillary Thyroid Cancer
Ármós Richárd Levente
KÁROLY RÁCZ CONSERVATIVE MEDICINE PROGRAM
Dr. Reusz György
SE Belgyógyászati és Onkológiai Klinika tanterme
2025-08-01 14:00:00
Molecular Genetics, Pathomechanism and Clinical Aspects of Metabolic Disorders
Dr. Lakatos Péter
Dr. Lakatos Péter András
Dr. Bödör Csaba
Dr. Kovács Gábor
Dr. Benyó Zoltán
Dr. Dános Kornél
Dr. Hubina Erika
PTC, the most common subtype of thyroid cancer, exhibits unique molecular and genetic alterations that are crucial to its pathogenesis and prognosis. Despite its generally favorable outcomes due to effective treatments such as thyroidectomy and RAI therapy, PTC often necessitates second-line therapies in cases where complete eradication of the tumor is challenging. Molecular profiling, particularly the identification of miRNA dysregulations and gene fusion mutations, has emerged as a promising possibility for refining diagnostic, prognostic, and therapeutic approaches to the disease.
In our studies, we employed advanced molecular diagnostics, mainly NGS, to comprehensively investigate miRNA expression patterns and fusion mutations and their relation to other clinically measurable variables in PTC. Through the analysis of 118 thyroid tissue sample pairs originating from PTC patients, we identified 30 significantly dysregulated miRNAs, including upregulated miRNAs such as miR-551b, miR-146b, miR-221, miR-222, and miR-375, as well as downregulated ones like miR-873 and miR-204. Pathway enrichment analyses revealed links between these miRNA deviations and critical biological processes, such as cellular responses to growth factor stimuli and HIF-1 signaling. Furthermore, our research uncovered 352 associations between certain miRNAs and clinicopathological variables, emphasizing their potential as biomarkers for PTC diagnosis, prognosis, and even therapeutic targeting.
In parallel, we analyzed fusion mutations in 100 different PTC samples applying NGS again. Fusion mutations were detected in 27% of cases, involving nine gene types, such as RET, and NTRK3. Notable associations were identified between certain fusions and clinicopathological factors. For instance, certain fusions were linked to the patients’ age, the size of the tumor, the type of thyroid surgery, or other elements in the medical history.
Our findings provide a deeper understanding of the molecular mechanisms driving PTC, offer potential biomarkers in diagnostics and prognostics, and highlight the value of integrating molecular profiling into routine PTC management. Our data could benefit surgical planning and other therapeutic strategies. These results support the need for the earlier molecular profiling of PTC patients. Together, these approaches have the potential to contribute to personalized medicine and improve clinical outcomes overall.
