Genetic mutations and prognostic indicators in differentiated thyroid cancer: a molecular perspective

The aim of this study was to investigate the relationship between the presence of the BRAF, HRAS, NRAS, and KRAS gene mutations and the development of dedifferentiation (iodine-refractory disease) and extrathyroidal disease in patients with differentiated thyroid carcinoma (DTC).

The patient group included 77 adults classified as intermediate or high-risk according to the American Thyroid Association's 2015 guidelines who underwent total thyroidectomy followed by radioiodine I-131 (RAI) therapy between June 2014 and December 2022. Clinical data were collected via the hospital information system, including the number of surgeries and RAI treatments and the levels of thyroglobulin (Tg), anti-thyroglobulin, and thyroid-stimulating hormone. The histopathological subtypes of DTC were reevaluated, and mutation analyses of the BRAF, KRAS, NRAS, and HRAS genes were performed using real-time polymerase chain reaction (PCR). Statistical analyses were conducted using Medcalc software, with p < 0.05 considered significant.

Of the 77 patients, most had classical papillary thyroid carcinoma, while others represented various subtypes. No mutations were found in BRAF K601E/V600_K601, KRAS G12x-G13D, or NRAS G12-G13; however, NRAS Q61x was found in one patient, HRAS Q61x in 12, and BRAFV600E/Ec in 36. A significant relationship was observed between HRAS Q61x mutation and disease response, alongside a significant association between gene mutations and iodine-refractory disease development (p = 0.0004). A ROC curve analysis indicated a 49.2 ng/mL threshold for Tg with 75% sensitivity and 94.1% specificity.

The findings suggest that the HRAS Q61x gene mutation is significantly associated with iodine-resistant disease. It may serve as a prognostic biomarker in early-stage thyroid cancer and aid in disease monitoring in metastatic patients.