The ability of anexelekto (AXL) expression and TERT promoter mutation to predict radioiodine-refractory differentiated thyroid carcinoma.

IF 2.4 3区医学 Q2 PATHOLOGY

Diagnostic Pathology Pub Date : 2025-04-16 DOI:10.1186/s13000-025-01643-0

Hasrayati Agustina, Tutik Nur Ayni, Yohana Azhar, Erwin Affandi Soeriadi, Bethy Suryawathy Hernowo

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引用次数: 0

Abstract

Background: Differentiated thyroid carcinoma (DTC) generally has a favourable prognosis with standard treatments; however, the risks of local recurrence and distant metastases remain a concern, affecting a substantial proportion of patients. Radioactive iodine (RAI) refractoriness further complicates DTC management, leading to substantially reduced survival rates. In this study, we aimed to identify anexelekto (AXL) expression and TERT promoter mutation as potential predictors of RAI-refractory DTC.

Methods: We conducted a retrospective analysis of 81 DTC patients who underwent thyroidectomy and received at least two courses of RAI therapy. After a median follow-up period of 30 months (range: 6-60 months), therapy response was categorized as nonrefractory or refractory. AXL expression and TERT promoter mutation were evaluated in all patients to discern any associations with the development of RAI refractoriness.

Results: The overall prevalence of refractory RAI in DTC patients was 44.4% (36/81). AXL expression was high in 30/36 patients (83.3%) with RAI-refractory DTC and negative/low in 24/45 patients (53.3%) with non-RAI-refractory DTC (OR adjusted: 44.98, CI 95%: 1.41-1439.03, p = 0.031). TERT promoter mutation occurred in 21/36 (58.3%) RAI-refractory DTCs and in 2/45 (4.4%) non-RAI-refractory DTCs (OR adjusted: 10.95, CI 95%: 1.06-112.92, p = 0.044). Despite similar age, sex, and histological type distributions between the RAI-refractory and non-RAI-refractory groups, significant differences in clinicopathological characteristics emerged. Multivariate analysis confirmed that aggressive subtype, elevated AXL expression, and TERT promoter mutation independently correlated with RAI-refractory status.

Conclusions: Our predictive model highlights the association of elevated AXL expression, TERT promoter mutation, and an aggressive tumour subtype with the risk of RAI refractoriness. This information has the potential to aid in making informed treatment decisions. Furthermore, AXL is a potential therapeutic target for RAI-refractory disease.

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anexelekto （AXL）表达和TERT启动子突变预测放射性碘难治性分化甲状腺癌的能力。

背景：分化型甲状腺癌（DTC）经标准治疗后预后良好；然而，局部复发和远处转移的风险仍然令人担忧，影响了相当一部分患者。放射性碘（RAI）的难治性进一步使DTC的治疗复杂化，导致生存率大大降低。在这项研究中，我们旨在确定anexelekto （AXL）表达和TERT启动子突变作为rai难治性DTC的潜在预测因子。方法：我们对81例接受甲状腺切除术并接受至少两个疗程RAI治疗的DTC患者进行了回顾性分析。中位随访期为30个月（范围：6-60个月）后，治疗反应分为非难治性或难治性。在所有患者中评估AXL表达和TERT启动子突变，以辨别与RAI难治性发展的任何关联。结果：DTC患者难治性RAI总发生率为44.4%（36/81）。在rai难治性DTC患者中，30/36例AXL表达高（83.3%），非rai难治性DTC患者中，24/45例AXL表达低（53.3%）（调整后OR: 44.98, CI 95%: 1.41 ~ 1439.03, p = 0.031）。TERT启动子突变发生在21/36（58.3%）赖氨酸难治性dtc和2/45（4.4%）非赖氨酸难治性dtc中（OR校正：10.95,CI 95%: 1.06-112.92, p = 0.044）。尽管在rai -难治性和非rai -难治性组之间存在相似的年龄、性别和组织类型分布，但在临床病理特征上存在显著差异。多因素分析证实，侵袭性亚型、AXL表达升高和TERT启动子突变与rai难治状态独立相关。结论：我们的预测模型强调了AXL表达升高、TERT启动子突变和侵袭性肿瘤亚型与RAI难治性风险的关联。这些信息有可能有助于做出明智的治疗决定。此外，AXL是rai难治性疾病的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diagnostic Pathology 医学-病理学

CiteScore

4.60

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Diagnostic Pathology is an open access, peer-reviewed, online journal that considers research in surgical and clinical pathology, immunology, and biology, with a special focus on cutting-edge approaches in diagnostic pathology and tissue-based therapy. The journal covers all aspects of surgical pathology, including classic diagnostic pathology, prognosis-related diagnosis (tumor stages, prognosis markers, such as MIB-percentage, hormone receptors, etc.), and therapy-related findings. The journal also focuses on the technological aspects of pathology, including molecular biology techniques, morphometry aspects (stereology, DNA analysis, syntactic structure analysis), communication aspects (telecommunication, virtual microscopy, virtual pathology institutions, etc.), and electronic education and quality assurance (for example interactive publication, on-line references with automated updating, etc.).