基于GC-MS的慢性髓系白血病代谢轮廓分析

发布时间：2018-04-20 09:55

本文选题：慢性髓系白血病 + 代谢组学　；参考：《中国实验血液学杂志》2017年06期

【摘要】：目的:应用基于气相色谱-质谱联用(GC-MS)的代谢组学方法对慢性髓系白血病(CML)患者血浆进行代谢轮廓分析,寻找与疾病相关的潜在标志物,并初步探讨其涉及的相关代谢通路。方法:选取2015年2月至2015年4月在苏州大学附属第一医院初次确诊的26例CML患者,及26例同期异基因造血干细胞供者(健康对照),另取26例经过一代酪氨酸激酶抑制剂(TKI)治疗后获得最佳疗效的CML患者(治疗后对照)。应用气相色谱质谱联用技术(GC-MS)方法对三组血浆样本进行代谢物无靶标检测,采集代谢物指纹图谱,结合模式识别分析方法及t检验筛选差异代谢物,通过受试者工作曲线(receiver operating characteristic curve,ROC)分析,评价差异代谢物临床效能,并进行Met PA代谢通路分析。结果:健康人及初诊CML患者血浆代谢表型明显不同。与健康对照组比较,CML组有6个血浆代谢物表现出差异,肉豆蔻酸、甘油丰度均较健康对照组低,而肌醇、半乳糖、乳酸、甘氨酸丰度均较健康对照组高(VIP1,P0.05,AUC0.7),经过TKI药物治疗后获得最佳疗效的CML患者上述差异血浆代谢物均有向正常人水平恢复的趋势。以上CML患者血浆代谢紊乱通路主要与半乳糖代谢、丙酮酸代谢、甘油酯代谢、甘氨酸丝氨酸苏氨酸代谢相关(影响值0.10)。结论:CML患者血浆中代谢物水平出现显著变化,代谢组学结合模式识别分析方法可能成为CML辅助诊断的新方法。
[Abstract]:Objective: to analyze the plasma metabolic profile of patients with chronic myeloid leukemia (CML) by GC-MS-based method, and to find out the potential markers associated with the disease and to explore the related metabolic pathways. Methods: from February 2015 to April 2015, 26 patients with CML were first diagnosed in the first affiliated Hospital of Suzhou University. And 26 allogeneic hematopoietic stem cell donors (healthy control group) and 26 CML patients (control group) who were treated with tyrosine kinase inhibitor (TKI). Gas chromatography-mass spectrometry (GC-MS) method was used to detect metabolites in three groups of plasma samples without target, to collect fingerprints of metabolites, and to screen different metabolites by pattern recognition analysis and t-test. The clinical efficacy of differential metabolites was evaluated by receiver operating characteristic curve analysis and Met PA metabolic pathway was analyzed. Results: plasma metabolic phenotypes were significantly different between healthy and newly diagnosed CML patients. Compared with the healthy control group, there were 6 plasma metabolites in CML group. The levels of myristic acid and glycerol were lower than those in the healthy control group, while inositol, galactose, lactic acid, The abundance of glycine was higher than that of the healthy control group. The plasma metabolites of the patients with CML who had the best curative effect after TKI treatment showed a tendency to recover to the normal level. The plasma metabolic disorder pathway in CML patients was mainly related to galactose metabolism, pyruvate metabolism, glycerol ester metabolism and glycine serine threonine metabolism. Conclusion there is a significant change in plasma metabolites in patients with CML, which may be a new method for the diagnosis of CML.
【作者单位】：苏州大学附属第一医院江苏省血液研究所苏州大学造血干细胞移植研究所卫生部血栓与止血重点实验室血液学协同创新中心;
【基金】：国家自然科学基金(81270617,81470346) 江苏高校优势学科建设工程资助项目(PAPD) 江苏省自然科学基金项目(BK20161204) 江苏省"333"工程人才资助江苏省六大高峰人才资助江苏省科教兴卫工程-临床医学中心(ZX201102) 江苏省血液病临床医学研究中心(江苏省科技厅生命健康专项-BL2012005) 国家临床重点专科建设项目江苏省创新能力建设专项(BM2015004)
【分类号】：R733.72

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