基于超高效液相色谱混合四级杆飞行时间质谱技术的代谢组学探讨不同背景下甲状腺癌的代谢机制  

Metabolic mechanisms of thyroid cancer in different background using ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry

作　　者：孙丹阳[1,6] 张玉洁 李雪 王丹[4] 韩蕊[5] 李宁 李亭苇[3] 赵雪 贾强[3] 谭建[3] 郑薇[3] 宋丽丽[5] 孟召伟[3] Sun Danyang;Zhang Yujie;Li Xue;Wang Dan;Han Rui;Li Ning;Li Tingwei;Zhao Xue;Jia Qiang;Tan Jian;Zheng Wei;Song Lili;Meng Zhaowei(Department of Nuclear Medicine,Tianjin Medical University General Hospital Airport Site,Tianjin 300308,China;Department of Pathology,Tianjin First Central Hospital,Tianjin 300190,China;Department of Nuclear Medicine,Tianjin Medical University General Hospital,Tianjin 300052,China;Department of Pathology,Tianjin Medical University General Hospital,Tianjin 300052,China;School of Traditional Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;Department of Nuclear Medicine,Tianjin Medical University,Tianjin 300203,China)

机构地区：[1]天津医科大学总医院空港医院核医学科,天津300308 [2]天津市第一中心医院病理科,天津300190 [3]天津医科大学总医院核医学科,天津300052 [4]天津医科大学总医院病理科,天津300052 [5]天津中医药大学中药学院,天津300193 [6]天津医科大学核医学科,天津300203

出　　处：《中华内分泌代谢杂志》2023年第9期751-758,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然基金项目(81971650);天津科技人才培育项目(KJ20059)。

摘　　要：目的分析正常背景及桥本甲状腺炎(Hashimoto′s thyroiditis, HT)背景下甲状腺乳头状癌(papillary thyroid cancer, PTC)代谢机制的异同, 探索HT与PTC的关系。方法本研究纳入样本匹配自天津医科大学总医院2018年1月至2019年1月期间实行甲状腺切除术, 病理结果证实为伴有HT背景下PTC组织及其癌旁组织样本31例(HT组), 正常背景下PTC组织及癌旁组织样本30例(NC组)。应用超高效液相色谱混合四级杆飞行时间质谱(ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry, UPLC-Q-TOF-MS)技术对样本进行数据采集, 比较2组间代谢产物的异同, 筛选不同背景下PTC的代谢机制异同, 通过Metabo-Analyst 5.0进行代谢通路分析, 探索相关代谢通路。结果 HT组和NC组筛选出7种相同的差异代谢物, 包括精氨酸、谷氨酸、半胱氨酸、柠檬酸、苹果酸、尿嘧啶和牛磺酸, 结合这7种生物标志物的受试者工作特征(receiver operating characteristic, ROC)曲线分析对PTC具有良好的鉴别性(HT组及NC组ROC曲线下面积值分别为0.867和0.973);2组共同的代谢通路为牛磺酸和次牛磺酸代谢, 精氨酸生物合成, 丙氨酸、天冬氨酸和谷氨酸代谢, 精氨酸和脯氨酸代谢, 以及谷氨酰胺和谷氨酸代谢。HT组特异的通路为氨酰基tRNA生物合成, 甘氨酸、丝氨酸和苏氨酸代谢。结论正常背景或HT背景在甲状腺癌中的代谢谱中有重要的异同。HT背景下PTC特异的通路为氨酰tRNA的生物合成及甘氨酸、丝氨酸和苏氨酸的代谢。Objective To analyze the metabolic mechanism of papillary thyroid cancer(PTC)in normal and Hashimoto′s thyroiditis(HT)background,and to explore the relationship between HT and PTC.Methods This study included a matched sample set collected from Tianjin Medical University General Hospital between January 2018 and January 2019,consisting of PTC and paracancular tissue from 31 cases with coexisting HT(HT group),and 30 cases without(NC group),all confirmed pathologically following thyroidectomy.The ultra-high performance liquid chromatography combined with mixed four-stage poles time-of-flight mass spectrometry(UPLC-Q-TOF-MS)was employed to acquire data from the samples.Metabolite differences between the two groups were compared,aiming to identify distinct metabolic mechanisms of PTC under different backgrounds.Metabolic pathway analysis was conducted using Metabo-Analyst 5.0 to explore relevant metabolic pathways.Results The HT group and NC group shared 7 common differentially expressed metabolites,including arginine,glutamic acid,cysteine,citric acid,malic acid,uracil,and taurine.Logistic regression model combined with receiver operating characteristic(ROC)analysis of these 7 biomarkers yielded excellent discriminatory capacity for PTC(area under ROC curve of HT group and NC group were 0.867 and 0.973,respectively).The common metabolic pathways were taurine and hypotaurine metabolism,arginine biosynthesis,alanine,aspartic acid and glutamic acid metabolism,arginine and proline metabolism,and glutamine and glutamic acid metabolism.The specific metabolic pathways in HT group were aminoacyl tRNA biosynthesis,glycine,serine,and threonine metabolism.Conclusion The metabolic profiles of thyroid cancer exhibit significant differences between cases with normal backgrounds and those with HT.The specific pathways for PTC and HT are aminoacyl tRNA biosynthesis and the metabolism of glycine,serine,and threonine.

关 键 词：代谢组学 桥本甲状腺炎 甲状腺乳头状癌 代谢通路 生物标志物 

分 类 号：R736.1[医药卫生—肿瘤]