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代谢组学分析鉴定赖氨酸和牛磺酸为 AML-M2 患者的候选预后生物标志物。

Metabolomics analysis identifies lysine and taurine as candidate prognostic biomarkers for AML-M2 patients.

机构信息

Phase I Clinical Trials Unit, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321#, Gulou district, Nanjing, 210008, China.

Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tongjia Avenue, Gulou District, Nanjing, 210008, China.

出版信息

Int J Hematol. 2020 Jun;111(6):761-770. doi: 10.1007/s12185-020-02836-7. Epub 2020 Feb 13.

Abstract

There is an ongoing search for potential biomarkers for acute myeloid leukemia (AML) patients using metabolic analysis. However, only few studies to date have focused on bone marrow samples or a specific subtype of AML. In the present study, we used gas chromatography time-of-flight mass spectrometry of plasma and bone marrow supernatants to compare the metabolic characteristics of patients with AML with maturation (AML-M2). This approach identified significantly altered metabolites. We next performed pathway analysis and determined relative mRNA expression by qRT-PCR. Our results show that lysine, methionine and serine were significantly decreased in AML-M2 patients compared with healthy control. Moreover, plasma abundance of lysine was negatively associated with patients' risk stratification. Taurine had higher plasma abundance in AML-M2 patients and plasma level of taurine was positively related with AML-M2 risk status, while the expression level of taurine transporter showed a negative correlation. Receiver operating characteristic curve analysis showed these four metabolites had high diagnostic value with lysine showing the highest sensitivity and specificity. These results suggest that plasma abundances of lysine and taurine may serve as potential metabolic biomarkers for the prognosis of patients with AML-M2.

摘要

目前,研究人员正在通过代谢分析寻找急性髓系白血病(AML)患者的潜在生物标志物。然而,迄今为止,只有少数研究集中在骨髓样本或 AML 的特定亚型上。在本研究中,我们使用气相色谱飞行时间质谱法分析了血浆和骨髓上清液,以比较成熟型 AML(AML-M2)患者的代谢特征。该方法确定了明显改变的代谢物。然后,我们进行了途径分析,并通过 qRT-PCR 测定了相对 mRNA 表达。我们的结果表明,与健康对照组相比,AML-M2 患者的赖氨酸、蛋氨酸和丝氨酸显著降低。此外,血浆赖氨酸丰度与患者的危险分层呈负相关。在 AML-M2 患者中,牛磺酸的血浆丰度更高,而牛磺酸的血浆水平与 AML-M2 的危险状态呈正相关,而牛磺酸转运蛋白的表达水平呈负相关。受试者工作特征曲线分析表明,这四种代谢物具有较高的诊断价值,其中赖氨酸的敏感性和特异性最高。这些结果表明,血浆赖氨酸和牛磺酸的含量可能是 AML-M2 患者预后的潜在代谢标志物。

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