Özçevik Halim, Öner Tamam Müge, Babacan Gündüzalp Buğrahan, Şengiz Erhan Selma, Acar Tayyar Merve Nur, Ertürk Biray
Department of Nuclear Medicine, Hamidiye Medical Faculty, University of Health Sciences, İstanbul, Turkiye.
Department of Nuclear Medicine, Prof. Dr. Cemil Taşcıoğlu City Hospital, University of Health Sciences, İstanbul, Turkiye.
Turk J Med Sci. 2024 Dec 25;55(1):72-81. doi: 10.55730/1300-0144.5944. eCollection 2025.
BACKGROUND/AIM: 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.
背景/目的：本研究旨在探讨BRAF、HRAS、NRAS和KRAS基因突变的存在与分化型甲状腺癌（DTC）患者去分化（碘难治性疾病）和甲状腺外疾病发生之间的关系。
患者组包括77名根据美国甲状腺协会2015年指南分类为中危或高危的成年人，他们在2014年6月至2022年12月期间接受了全甲状腺切除术，随后接受碘-131（RAI）治疗。通过医院信息系统收集临床数据，包括手术次数和RAI治疗次数以及甲状腺球蛋白（Tg）、抗甲状腺球蛋白和促甲状腺激素水平。对DTC的组织病理学亚型进行重新评估，并使用实时聚合酶链反应（PCR）对BRAF、KRAS、NRAS和HRAS基因进行突变分析。使用Medcalc软件进行统计分析，p<0.05被认为具有统计学意义。
77例患者中，大多数为经典型乳头状甲状腺癌，其他为各种亚型。在BRAF K601E/V600_K601、KRAS G12x-G13D或NRAS G12-G13中未发现突变；然而，在1例患者中发现NRAS Q61x，12例中发现HRAS Q61x，36例中发现BRAFV600E/Ec。观察到HRAS Q61x突变与疾病反应之间存在显著关系，同时基因突变与碘难治性疾病发生之间存在显著关联（p = 0.0004）。ROC曲线分析表明，Tg阈值为49.2 ng/mL时，敏感性为75%，特异性为94.1%。
研究结果表明，HRAS Q61x基因突变与碘抵抗性疾病显著相关。它可能作为早期甲状腺癌的预后生物标志物，并有助于转移性患者的疾病监测。
