Turkish Journal of Medical Sciences
Abstract
Background/aim: This study aimed to investigate the relationship between the presence of 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).Materials and methods: Seventy-seven adult patients classified as intermediate and high-risk according to the ATA 2015 guidelines, who underwent total thyroidectomy followed by radioiodine I-131(RAI) therapy between June 2014 and December 2022, were included. Clinical data were collected via the hospital information system, including the number of surgeries, RAI treatments, and levels of thyroglobulin(Tg), anti-thyroglobulin, and thyroid-stimulating hormone. Histopathological subtypes of DTC were re-evaluated, and mutation analyses of BRAF, KRAS, NRAS, and HRAS genes were performed using real-time polymerase chain reaction (PCR). Statistical analyses were conducted using Medcalc software, with p-values <0.05 considered significant.Results: 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). ROC curve analysis indicated a 49.2 ng/ml threshold for Tg with 75% sensitivity and 94.1% specificity.Conclusion: Our findings suggest that the HRAS Q61x gene mutation is significantly associated with iodine-resistant disease and may serve as a prognostic biomarker in early-stage thyroid cancer and aid in disease monitoring in metastatic patients.
Author ORCID Identifier
HALİM ÖZÇEVİK: 0000-0001-7201-9868
MÜGE TAMAM: 0000-0002-3793-0178
GÜNDÜZALP BABACAN: 0000-0002-0561-5739
SELMA ŞENGİZ ERHAN: 0000-0001-8810-8806
BİRAY ERTÜRK: 0000-0002-0348-6267
MERVE ACAR TAYYAR: 0009-0001-4126-7778
DOI
10.55730/1300-0144.5944
Keywords
BRAF, Differentiated thyroid cancer, gene mutation, iodine-refractory disease, prognostic biomarkers, RAS
First Page
72
Last Page
81
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
ÖZÇEVİK, HALİM; TAMAM, MÜGE ÖNER; BABACAN, GÜNDÜZALP BUĞRAHAN; ŞENGİZ ERHAN, SELMA; ACAR TAYYAR, MERVE NUR; and ERTÜRK, BİRAY
(2025)
"Genetic mutations and prognostic indicators in differentiated thyroid cancer: a molecular perspective,"
Turkish Journal of Medical Sciences: Vol. 55:
No.
1, Article 8.
https://doi.org/10.55730/1300-0144.5944
Available at:
https://journals.tubitak.gov.tr/medical/vol55/iss1/8
