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基于GC-MS的慢性髓系白血病代謝輪廓分析

發(fā)布時間:2018-04-20 09:55

  本文選題:慢性髓系白血病 + 代謝組學 ; 參考:《中國實驗血液學雜志》2017年06期


【摘要】:目的:應用基于氣相色譜-質譜聯(lián)用(GC-MS)的代謝組學方法對慢性髓系白血病(CML)患者血漿進行代謝輪廓分析,尋找與疾病相關的潛在標志物,并初步探討其涉及的相關代謝通路。方法:選取2015年2月至2015年4月在蘇州大學附屬第一醫(yī)院初次確診的26例CML患者,及26例同期異基因造血干細胞供者(健康對照),另取26例經過一代酪氨酸激酶抑制劑(TKI)治療后獲得最佳療效的CML患者(治療后對照)。應用氣相色譜質譜聯(lián)用技術(GC-MS)方法對三組血漿樣本進行代謝物無靶標檢測,采集代謝物指紋圖譜,結合模式識別分析方法及t檢驗篩選差異代謝物,通過受試者工作曲線(receiver operating characteristic curve,ROC)分析,評價差異代謝物臨床效能,并進行Met PA代謝通路分析。結果:健康人及初診CML患者血漿代謝表型明顯不同。與健康對照組比較,CML組有6個血漿代謝物表現(xiàn)出差異,肉豆蔻酸、甘油豐度均較健康對照組低,而肌醇、半乳糖、乳酸、甘氨酸豐度均較健康對照組高(VIP1,P0.05,AUC0.7),經過TKI藥物治療后獲得最佳療效的CML患者上述差異血漿代謝物均有向正常人水平恢復的趨勢。以上CML患者血漿代謝紊亂通路主要與半乳糖代謝、丙酮酸代謝、甘油酯代謝、甘氨酸絲氨酸蘇氨酸代謝相關(影響值0.10)。結論:CML患者血漿中代謝物水平出現(xiàn)顯著變化,代謝組學結合模式識別分析方法可能成為CML輔助診斷的新方法。
[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.
【作者單位】: 蘇州大學附屬第一醫(yī)院江蘇省血液研究所蘇州大學造血干細胞移植研究所衛(wèi)生部血栓與止血重點實驗室血液學協(xié)同創(chuàng)新中心;
【基金】:國家自然科學基金(81270617,81470346) 江蘇高校優(yōu)勢學科建設工程資助項目(PAPD) 江蘇省自然科學基金項目(BK20161204) 江蘇省"333"工程人才資助 江蘇省六大高峰人才資助 江蘇省科教興衛(wèi)工程-臨床醫(yī)學中心(ZX201102) 江蘇省血液病臨床醫(yī)學研究中心(江蘇省科技廳生命健康專項-BL2012005) 國家臨床重點?平ㄔO項目 江蘇省創(chuàng)新能力建設專項(BM2015004)
【分類號】:R733.72

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