【摘要】 目的:基于超高效液相色谱-质谱(UPLC-MS)分析平台的非靶向代谢组学，研究多发性骨髓瘤(MM)患者的代谢特征，探索影响MM发生、发展的代谢相关潜在新机制。方法:以42例MM患者[包括21例初诊(ND)、21例复发(RP)]及21例年龄、性别与MM患者相匹配的同期健康志愿者(HC)作为研究对象。采用UPLC-MS分析平台对研究对象血清中的小分子代谢物进行检测，使用主成分分析(PCA)和正交偏最小二乘判别法(OPLS-DA)及200次置换检验等数学模型分析各组间的代谢轮廓差异。在人类代谢组数据库中完成差异代谢物的鉴定，并使用KEGG数据库进行异常代谢途径分析。结果:MM患者与健康志愿者的代谢轮廓无论在PCA模型还是OPLS-DA模型中均表现为显著分离，而初诊与复发MM患者的代谢轮廓仅在OPLS-DA模型中分离显著。在ND对比HC、RP对比HC和RP对比ND 3个比较队列中，分别鉴定出19、24、18种差异代谢物，主要为鞘脂类、甘油磷脂类和脂酰氨基酸类物质。相对于健康人群，初诊和复发MM患者的异常代谢途径主要表现在鞘脂代谢和甘油磷脂代谢；相较于初诊患者，复发MM患者主要表现为鞘脂代谢和醚脂代谢途径异常。结论:MM患者与健康人群的代谢轮廓存在显著差异，复发与初诊MM患者的代谢轮廓相近但仍存在一定的差异；甘油磷脂、鞘脂、醚脂代谢途径可能在MM的发生、发展中发挥着重要的生物学作用。更多还原

【Abstract】 Objective:Non-targeted metabolomics based on ultra-performance liquid chromatography mass spectrometry(UPLC-MS) platform was used to study the metabolic characteristics of multiple myeloma(MM)patients,and explore potential new metabolic mechanisms affecting the occurrence and development of MM.Methods:The study enrolled 42 MM patients,including 21 newly diagnosed(ND) patients and 21 relapsed patients(RP),and 21age-sex matched healthy controls(HC) as subjects.UPLC-MS analysis platform was used to detect small molecule metabolites in serum of the subjects.Principal component analysis(PCA),orthogonal partial least-squared discriminant analysis(OPLS-DA) and 200 random permutations were used to analyze the differences of metabolic profiles among groups.Identification of differential metabolites was completed in the Human Metabolome Database(HMDB) and abnormal metabolic pathway analysis was performed using the KEGG database.Results:The metabolic profiles of MM patients and healthy controls were significantly separated in both PC A and OPLS-DA models,while the metabolic profiles of newly diagnosed and relapsed MM patients were significantly separated only in OPLS-DA model.In ND vs HC,RP vs HC and RP vs ND cohorts,19,24 and 18 differential metabolites were identified respectively,mainly sphingolipids,glycerophospholipids and fatty acyl amino acids.The metabolic pathway abnormalities in newly diagnosed and relapsed MM patients were mainly manifested in sphingolipid metabolism and glycerophospholipid metabolism compared to healthy controls.Compared with newly diagnosed MM patients,relapsed MM patients were mainly manifested in sphingolipid metabolism and ether-lipid metabolism.Conclusion:The metabolic profiles of MM patients are significantly different from those of healthy people.Relapsed MM patients and newly diagnosed MM patients have similar metabolic profiles,but there are still some differences.Glycerophospholipid metabolism,sphingolipid metabolism and ether-lipid metabolism may play important biological roles in the occurrence and development of MM.更多还原