Mohamad Pakarulrazy Nur Fadhlina, Abu Nadiah, Abdullah Suhaimi Shahrun Niza, Paisol Nadzlee Harith, Md Zin Reena Rahayu, MdLatar Nani H, Ab Mutalib Nurul Syakima
UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, MYS.
Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, MYS.
Cureus. 2025 Jun 29;17(6):e87001. doi: 10.7759/cureus.87001. eCollection 2025 Jun.
BACKGROUND/AIM: Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer (TC) and is generally associated with a favorable prognosis. Nevertheless, aggressive variants of PTC that exhibit metastasis and resistance to radioiodine (RAI) therapy present significant clinical challenges. This study sought to generate a preliminary dataset on gene expression in RAI-refractory PTC using microarray analysis.
Fresh frozen thyroid tissues were collected from PTC patients without lymph node metastasis and RAI avidity (n = 5), PTC patients with lymph node metastasis and RAI refractoriness (n = 5), and adjacent normal thyroid tissues (n = 4). The samples were cryosectioned, stained with hematoxylin and eosin, and confirmed by a pathologist. Nucleic acids were extracted using the AllPrep DNA/RNA/miRNA Universal Kit (Qiagen, Germany), and RNA quantity, purity, and integrity were assessed. RNA samples were amplified, labelled using the Agilent Low Input Quick Amp Labeling Kit (Agilent Technologies, Santa Clara, CA, US), and purified using the RNeasy Mini Kit (Qiagen). Cy3-labelled cRNA was fragmented and hybridized to Agilent SurePrint G3 Human GE v3 8 × 60 K microarray slides. Data were analyzed using AltAnalyze software and the iDEP web application.
Our results revealed distinct expression patterns between RAI-avid and RAI-refractory PTC, with significant downregulation observed in key thyroid hormone synthesis genes, such as , , and , across both groups. Notably, showed a variable expression pattern, suggesting its complex role in PTC pathophysiology. Pathway analysis highlighted the disruption of metabolic and immune-related pathways, emphasizing the altered physiological state of RAI-refractory PTC.
This study provides essential insights into the molecular underpinnings of RAI resistance in PTC and offers a foundation for future research aimed at developing targeted therapies that could enhance treatment efficacy and patient outcomes.
背景/目的：甲状腺乳头状癌（PTC）是甲状腺癌（TC）最常见的形式，通常预后良好。然而，表现出转移和对放射性碘（RAI）治疗耐药的侵袭性PTC变体带来了重大的临床挑战。本研究旨在通过微阵列分析生成关于RAI难治性PTC基因表达的初步数据集。
收集无淋巴结转移且对RAI有摄取的PTC患者（n = 5）、有淋巴结转移且对RAI难治的PTC患者（n = 5）以及相邻正常甲状腺组织（n = 4）的新鲜冷冻甲状腺组织。将样本进行冷冻切片，用苏木精和伊红染色，并由病理学家确认。使用AllPrep DNA/RNA/miRNA通用试剂盒（德国Qiagen公司）提取核酸，并评估RNA的数量、纯度和完整性。RNA样本进行扩增，使用安捷伦低输入快速扩增标记试剂盒（美国加利福尼亚州圣克拉拉市安捷伦科技公司）进行标记，并用RNeasy Mini试剂盒（Qiagen公司）进行纯化。Cy3标记的cRNA片段化后与安捷伦SurePrint G3人类基因表达v3 8×60 K微阵列玻片杂交。使用AltAnalyze软件和iDEP网络应用程序分析数据。
我们的结果揭示了RAI摄取型和RAI难治型PTC之间不同的表达模式，在两组中关键甲状腺激素合成基因，如 、 和 ，均显著下调。值得注意的是， 表现出可变的表达模式，表明其在PTC病理生理学中的复杂作用。通路分析突出了代谢和免疫相关通路的破坏，强调了RAI难治型PTC改变的生理状态。
本研究为PTC中RAI耐药的分子基础提供了重要见解，并为未来旨在开发可提高治疗效果和患者预后的靶向治疗的研究奠定了基础。
