Department of Endocrinology, Jiangyin People's Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu 214400, P.R. China.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Int J Mol Med. 2018 May;41(5):3006-3014. doi: 10.3892/ijmm.2018.3494. Epub 2018 Feb 16.
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new insights into detailed metabolic changes of PTC, and hold great potential in the treatment of PTC.
甲状腺癌是最常见的甲状腺癌。基于磁共振（NMR）的代谢组学技术是代谢物结构解析的金标准，与其他代谢组学技术相比，可以提供不同的信息覆盖范围。在这里，我们首先进行了基于 NMR 的代谢组学研究，以详细研究代谢变化，特别是与 PTC 发病机制相关的代谢途径变化。采用 1H NMR 代谢组学技术结合多变量分析，分析了从 16 名患者中获得的配对肿瘤和正常甲状腺组织。结果进一步用京都基因与基因组百科全书（KEGG）和人类代谢组数据库注释，然后使用 MetaboAnalyst 3.0 的途径分析模块和富集分析模块进行分析。基于分析技术，我们建立了主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交偏最小二乘判别分析（OPLS-DA）的模型，这些模型能够区分 PTC 与正常甲状腺组织，并从两个 OPLS-DA 模型中发现 15 个稳健的差异代谢物。我们通过通路分析和富集分析分别确定了 8 个 KEGG 通路和 3 个小分子通路数据库通路与 PTC 显著相关，通过这些通路分析确定了与 PTC 相关的代谢物，包括支链氨基酸代谢（亮氨酸和缬氨酸）、其他氨基酸代谢（甘氨酸和牛磺酸）、糖酵解（乳酸）、三羧酸循环（柠檬酸）、胆碱代谢（胆碱、乙醇胺和甘油磷酸胆碱）和脂质代谢（极低密度脂蛋白和低密度脂蛋白）。总之，PTC 的特点是糖酵解增加，三羧酸循环受到抑制，致癌氨基酸增加，以及胆碱和脂质代谢异常。本研究的结果为 PTC 的详细代谢变化提供了新的见解，为 PTC 的治疗提供了很大的潜力。
