Alterations in the amino acid profile in patients with papillary thyroid carcinoma with and without Hashimoto’s thyroiditis

PURPOSE: Amino acids (AAs) play important physiological roles in living cells. Some amino acid changes in blood are specific for autoimmune disorders, and some are specific for thyroid cancer. The aims of this study were to profile AA metabolites in the serum of patients with papillary thyroid carcinoma (PTC0) without Hashimoto’s thyroiditis (HT) and patients with PTC with HT (PTC1) and predict whether AA metabolites are associated with thyroid disease, thyroid hormone and thyroid autoantibodies.
METHODS: A total of 93 serum samples were collected, including 28 healthy controls (HCs), 28 PTC0 patients and 37 PTC1 patients. Serum samples were analysed by high-performance liquid chromatography-triple stage quadrupole-mass spectrometry (HPLC-TSQ-MS), and 21 amino acids (AAs) were detected.
RESULTS: The serum concentration of glutamic acid was significantly elevated in PTC1 patients compared with PTC0 patients. Lysine was the second amino acid that differentiated these two groups of PTC patients. In addition, the serum concentrations of glycine, alanine and tyrosine were significantly reduced in both PTC patient groups compared to the HC group. These AAs were also correlated with thyroid hormones and antibodies. Five amino acid markers, namely, glycine, tyrosine, glutamic acid, glutamine and arginine, separated/distinguished PTC0 patients from healthy subjects, and eight AA markers, the same AAs as above without arginine but with alanine, leucine, valine and histidine, separated/distinguished PTC1 patients from healthy subjects based on ROC analysis.
CONCLUSION: Compared with the HCs, changes in AAs in PTC0 and PTC1 patients showed similar patterns, suggesting the possibility of a common pathophysiological basis, which confirms preliminary research that PTC is significantly associated with pathologically confirmed HT. We found two AAs, lysine and alanine, that can perform diagnostic functions in distinguishing PTC1 from PTC0.

研究目的：氨基酸（Amino acids, AAs）在活细胞中发挥重要生理功能。血液中部分氨基酸变化与自身免疫性疾病具有特异性关联，另有部分氨基酸变化可特异性提示甲状腺癌。本研究旨在对无桥本甲状腺炎（Hashimoto’s thyroiditis, HT）的乳头状甲状腺癌（papillary thyroid carcinoma, PTC0）患者、伴桥本甲状腺炎的乳头状甲状腺癌（PTC1）患者的血清氨基酸代谢物进行谱图分析，并探究氨基酸代谢物与甲状腺疾病、甲状腺激素及甲状腺自身抗体的相关性。
研究方法：本研究共收集93份血清样本，其中包括28名健康对照（healthy controls, HCs）、28例PTC0患者及37例PTC1患者。采用高效液相色谱-三重四极杆质谱（high-performance liquid chromatography-triple stage quadrupole-mass spectrometry, HPLC-TSQ-MS）对血清样本进行检测，共检出21种氨基酸。
研究结果：与PTC0患者相比，PTC1患者血清谷氨酸浓度显著升高；赖氨酸是区分这两组乳头状甲状腺癌患者的第二重要差异氨基酸。此外，与健康对照组相比，两组乳头状甲状腺癌患者的血清甘氨酸、丙氨酸及酪氨酸浓度均显著降低。上述氨基酸亦与甲状腺激素及抗体水平存在相关性。基于受试者工作特征曲线（Receiver Operating Characteristic, ROC）分析，筛选出5种氨基酸标志物（甘氨酸、酪氨酸、谷氨酸、谷氨酰胺及精氨酸），可有效区分PTC0患者与健康受试者；另有8种氨基酸标志物（除精氨酸外包含上述甘氨酸、酪氨酸、谷氨酸、谷氨酰胺，同时补充丙氨酸、亮氨酸、缬氨酸及组氨酸），可有效区分PTC1患者与健康受试者。
研究结论：与健康对照组相比，PTC0与PTC1患者的血清氨基酸变化模式具有相似性，提示二者可能存在共同的病理生理基础，这一结果验证了此前初步研究中「乳头状甲状腺癌与经病理证实的桥本甲状腺炎存在显著关联」的结论。本研究发现赖氨酸与丙氨酸这两种氨基酸可用于区分PTC1与PTC0患者，具备临床诊断价值。