Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.
Thyroid Surgery Department, Zhejiang Cancer Hospital, Hangzhou, 310022, Zhejiang, China.
Sci Rep. 2024 May 8;14(1):10546. doi: 10.1038/s41598-024-61067-6.
Radioiodine refractory (RAIR) patients do not benefit from iodine-131 therapy. Thus, timely identification of RAIR patients is critical for avoiding ineffective radioactive iodine therapy. In addition, determining the causes of iodine resistance will facilitate the development of novel treatment strategies. This study was comprised of 20 RAIR and 14 non-radioiodine refractory (non-RAIR) thyroid cancer patients. Liquid chromatography-mass spectrometry was used to identify differences in the serum metabolites of RAIR and non-RAIR patients. In addition, chemical assays were performed to determine the effects of the differential metabolites on iodine uptake. Metabolic pathway enrichment analysis of the differential metabolites revealed significant differences in the phenylalanine and tyrosine metabolic pathways. Notably, quinate and shikimic acid, metabolites of the tyrosine pathway, were significantly increased in the RAIR group. In contrast, the phenylalanine pathway metabolites, hippuric acid and 2-phenylacetamide, were markedly decreased in the RAIR group. Thyroid peroxidase plays an important role in catalyzing the iodination of tyrosine residues, while the ionic state of iodine promotes the iodination reaction. Quinate, shikimic acid, hippuric acid, and 2-phenylacetamide were found to be involved in the iodination of tyrosine, which is a key step in thyroid hormone synthesis. Specifically, quinate and shikimic acid were found to inhibit iodination, while hippuric acid and 2-phenylacetamide promoted iodination. Abnormalities in phenylalanine and tyrosine metabolic pathways are closely associated with iodine resistance. Tyrosine is required for thyroid hormone synthesis and could be a potential cause of iodine resistance.
放射性碘难治（RAIR）患者不会从碘-131 治疗中获益。因此，及时识别 RAIR 患者对于避免无效的放射性碘治疗至关重要。此外，确定碘抵抗的原因将有助于开发新的治疗策略。本研究纳入了 20 例 RAIR 和 14 例非放射性碘难治（non-RAIR）甲状腺癌患者。采用液相色谱-质谱联用技术鉴定 RAIR 和 non-RAIR 患者血清代谢物的差异。此外，还进行了化学测定以确定差异代谢物对碘摄取的影响。差异代谢物的代谢途径富集分析显示，苯丙氨酸和酪氨酸代谢途径存在显著差异。值得注意的是，RAIR 组中酪氨酸途径的代谢物奎宁酸和莽草酸明显增加。相比之下，RAIR 组中苯丙氨酸途径的代谢物马尿酸和 2-苯乙酰胺显著减少。甲状腺过氧化物酶在催化酪氨酸残基碘化中起重要作用，而碘的离子状态促进碘化反应。发现奎宁酸、莽草酸、马尿酸和 2-苯乙酰胺参与了酪氨酸的碘化，这是甲状腺激素合成的关键步骤。具体而言，奎宁酸和莽草酸被发现抑制碘化，而马尿酸和 2-苯乙酰胺促进碘化。苯丙氨酸和酪氨酸代谢途径的异常与碘抵抗密切相关。酪氨酸是甲状腺激素合成所必需的，可能是碘抵抗的潜在原因。
