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慢性心力衰竭患者血浆诊断生物标志物的代谢组学鉴定

Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure.

作者信息

Wang Juan, Li Zhongfeng, Chen Jianxin, Zhao Huihui, Luo Liangtao, Chen Chan, Xu Xuegong, Zhang Wenting, Gao Kuo, Li Bin, Zhang Junpeng, Wang Wei

机构信息

Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

Mol Biosyst. 2013 Nov;9(11):2618-26. doi: 10.1039/c3mb70227h.

Abstract

Chronic heart failure (CHF), as a progressive clinical syndrome, is characterized by failure of enough blood supply from the heart to meet the body's metabolic demands, and there is intense interest in identifying novel biomarkers that could make contributions to the diagnosis of CHF. Metabolomics, compared with current diagnostic approaches, could investigate many metabolic perturbations within biological systems. The overarching goal of the work discussed here is to apply a high-throughput approach to identify metabolic signatures and plasma diagnostic biomarkers underlying CHF by 1H-NMR spectroscopy. Plasma samples from 39 patients with CHF and 15 controls were analyzed by NMR spectroscopy. After processing the data, orthogonal partial least square discriminant analysis (OPLS-DA) was performed. The statistical model revealed good explained variance and predictability, and the diagnostic performance assessed by leave-one-out analysis exhibited 92.31% sensitivity and 86.67% specificity. The OPLS-DA score plots of spectra revealed good separation between case and control on the level of metabolites, and multiple biochemical changes indicated hyperlipidemia, alteration of energy metabolism and other potential biological mechanisms underlying CHF. It was concluded that the NMR-based metabolomics approach demonstrated good performance to identify diagnostic plasma markers and provided new insights into metabolic process related to CHF.

摘要

慢性心力衰竭(CHF)是一种进行性临床综合征,其特征是心脏供血不足,无法满足身体的代谢需求,因此人们对寻找有助于CHF诊断的新型生物标志物有着浓厚的兴趣。与目前的诊断方法相比,代谢组学可以研究生物系统内的许多代谢紊乱情况。本文所讨论工作的总体目标是应用高通量方法,通过1H-NMR光谱识别CHF潜在的代谢特征和血浆诊断生物标志物。对39例CHF患者和15例对照的血浆样本进行了NMR光谱分析。在对数据进行处理后,进行了正交偏最小二乘判别分析(OPLS-DA)。统计模型显示出良好的解释方差和可预测性,留一法分析评估的诊断性能表现出92.31%的敏感性和86.67%的特异性。光谱的OPLS-DA得分图显示,病例组和对照组在代谢物水平上有良好的分离,多种生化变化表明存在高脂血症、能量代谢改变以及CHF潜在的其他生物学机制。研究得出结论,基于NMR的代谢组学方法在识别诊断性血浆标志物方面表现良好,并为与CHF相关的代谢过程提供了新的见解。

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