基于HPLC/Q-TOF-MS的甲状腺乳头状癌组织代谢组学研究

目的：用组织代谢组学方法，探讨甲状腺乳头状癌（papillary thyroid carcinoma, PTC）组织及癌旁组织的代谢差异，寻找PTC的潜在生物标志物，探索PTC的发病机制与治疗策略。方法：收集2018年10月至2020年2月期间湖南省人民医院乳甲外科手术切除的40例PTC患者的癌组织及癌旁组织标本。利用HPLC-MS技术平台对PTC组织及癌旁组织样本的差异性代谢物进行多维统计分析，寻找与PTC相关的异常代谢通路。结果：经PCA、PLS-DA、OPLS-DA分析得知癌组织和癌旁组织的代谢轮廓具有显著性差异。经OPLS-Loading plot分析，结合VIP>1、FC>2，且P<0.05，筛选出76个潜在差异性代谢物。其中亮氨酸、2-褪黑素、香草酸等33种代谢物在PTC组织中表达上调；3-葡萄糖苷、甘油磷脂、磷脂酰胆碱、乳糖等43代谢物在PTC癌组织中表达下调。寻找到与差异性代谢物相关的13条异常代谢通路，如半胱氨酸与蛋氨酸代谢、与甘油磷脂代谢、嘧啶代谢、半乳糖代谢以及丙氨酸、天冬氨酸和谷氨酸代谢、柠檬酸循环等，这些代谢通路可能参与PTC代谢的病理生理过程。ROC曲线下面积大于0.9的差异性代谢物有5种，分别是庚二酸、糖醇、辛二酸、乳糖和L-丝氨酸。结论：PTC组织中半乳糖代谢和氨基酸代谢发生改变，PTC组织细胞中存在沃伯格效应(Warburg effect)。庚二酸、糖醇、辛二酸、乳糖、L-丝氨酸五种差异性代谢物可以用来区分PTC患者与正常人。

Research of tissue metabolomics in papillary thyroid carcinoma based on HPLC/Q-TOF-MS

Objective: To explore the metabolic differences between papillary thyroid carcinoma (PTC) tissues and adjacent tissues using tissue metabolomics methods, and to search for potential biomarkers of PTC as well as to explore the pathogenesis and treatment strategies for PTC. Methods: Collected cancer and para-cancerous tissue specim ens from 40 patients with PTC who had undergone breast surgery at D epartm ent of Breast and Thyroid Surgery of H unan Provincial People''s H ospital from O ctober 2018 to February 2020. Using the HPLC-MS technology platform, multi-dimensional statistical analysis of differential metabolites in PTC tissues and adjacent tissues was performed to find abnormal metabolic pathways related to PTC. Results: PCA, PLS-DA, OPLS-DA analyses showed that the metabolic profiles of cancer tissues and adjacent tissues were significantly different. OPLS-Loading plot analysis screened 76 potential differential metabolites (VIP>1, FC>2, and P<0.05). Among them, 33 metabolites such as Leucyl-phenylalanine,2-Oxomelatonin and Vanillactic acid were up-regulated in PTC tissues; 43 metabolites such as 3-glucoside, glycerophospholipid,phosphatidylcholine and lactose were down-regulated in PTC tissues. 13 abnormal metabolic pathways related to differential metabolites that may be involved in the pathophysiological process of PTC metabolism were found, such as: cysteine and methionine metabolism, glycerophospholipid metabolism, pyrimidine metabolism, galactose metabolism and alanine, aspartic acid and glutamic acid metabolism, citric acid cycle and so on. There were five types of differential metabolites with an area under the ROC curve greater than 0.9, namely pimelic acid, solerol, suberic acid, Alpha-Lactose and L-Serine. Conclusion: The galactose metabolism and amino acid metabolism in PTC tissues have changed, and Warburg effect exists in cells of PTC tissues. Pimelic acid, solerol, suberic acid,Alpha-Lactose and L-Serine can be used to distinguish PTC from normal people.