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通过血浆代谢组学分析鉴定不稳定型心绞痛的生物标志物

Identification of biomarkers for unstable angina by plasma metabolomic profiling.

作者信息

Sun Meng, Gao Xueqin, Zhang Dongwei, Ke Chaofu, Hou Yan, Fan Lijun, Zhang Ruoxi, Liu Haixia, Li Kang, Yu Bo

机构信息

Department of Epidemiology and Biostatistics, Public Health School, Harbin Medical University, 157 Baojian Road, Harbin 150081, China.

出版信息

Mol Biosyst. 2013 Dec;9(12):3059-67. doi: 10.1039/c3mb70216b. Epub 2013 Sep 24.

Abstract

Unstable angina (UA) is one of the most dangerous types of coronary heart disease and has high mortality and morbidity rates worldwide. However, the diagnostic accuracy for UA is unsatisfactory in clinical practice. In this study, we investigated the application of plasma metabolomics in discovering potential biomarkers for the diagnosis of UA. Plasma samples from 45 UA and 43 atherosclerosis (AS) in-patients were collected and analyzed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS) in both positive and negative ion modes. Good separations were observed between the UA patients and AS controls. Tandem mass spectrometry experiments were carried out to identify biomarker candidates that contributed most to the discrimination (VIP > 1.2 and p < 0.05). Sixteen potential endogenous biomarkers for UA were identified, and those could perform a satisfactory diagnostic accuracy for discrimination between UA and AS patients (AUC = 0.9143). In the UA patients compared to the AS controls, the plasma concentrations of 12 metabolites were higher while the concentrations of four metabolites were lower. In conclusion, our study demonstrated that plasma metabolomics analyzed by RRLC-QTOF/MS had great potential in biomarker discovery for UA. These biomarkers could not only be helpful for the diagnosis of patients with UA, but also provide more information for further understanding of the metabolic processes of UA.

摘要

不稳定型心绞痛(UA)是冠心病最危险的类型之一,在全球范围内具有较高的死亡率和发病率。然而,在临床实践中,UA的诊断准确性并不令人满意。在本研究中,我们调查了血浆代谢组学在发现UA诊断潜在生物标志物方面的应用。收集了45例UA患者和43例动脉粥样硬化(AS)患者的血浆样本,并使用快速分辨率液相色谱四极杆飞行时间质谱(RRLC-QTOF/MS)在正离子和负离子模式下进行分析。观察到UA患者与AS对照组之间有良好的分离效果。进行串联质谱实验以鉴定对鉴别贡献最大的生物标志物候选物(VIP>1.2且p<0.05)。鉴定出16种UA潜在内源性生物标志物,这些标志物对鉴别UA和AS患者具有令人满意的诊断准确性(AUC=0.9143)。与AS对照组相比,UA患者中有12种代谢物的血浆浓度较高,而4种代谢物的浓度较低。总之,我们的研究表明,通过RRLC-QTOF/MS分析的血浆代谢组学在UA生物标志物发现方面具有巨大潜力。这些生物标志物不仅有助于UA患者的诊断,还可为进一步了解UA的代谢过程提供更多信息。

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