Zhou Yubo, Wang Kai, Zeng Jun, Li Wei, Peng Jin, Zhou Zhiyuan, Deng Pengchi, Sun Mingwei, Yang Hao, Li Shijun, Lu Charles Damien, Jiang Hua
Department of Acute Care Surgery, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, Chengdu, China.
Metabolomics and Multidisciplinary Laboratory for Trauma Research, Institute for Emergency and Disaster Medicine, Chengdu, China.
Asia Pac J Clin Nutr. 2019;28(2):411-418. doi: 10.6133/apjcn.201906_28(2).0024.
By combining the techniques of metabolomics and computational biology, this research aims to explore the mechanism of metabolic dynamics in critically injured patients and develop a new early warning method for mortality.
A prospective cohort study was conducted, group plasma samples of critically injured patients were collected for 1H-NMR metabolomics analysis. The data was processed with partial least squares regression, to explore the role of enzyme-gene network regulatory mechanism in critically injured metabolic network regulation and to build a quantitative prediction model for early warning of fast death.
In total, 60 patients were enrolled. There were significant differences in plasma metabolome between the surviving patients and the deceased ones. Compared to the surviving patients, 112 enzymes and genes regulating the 6 key metabolic marker disturbances of neopterin, corticosterone, 3-methylhistidine, homocysteine, Serine, tyrosine, prostaglandin E2, tryptophan, testosterone and estriol, were observed in the plasmas of deceased ones. Among patients of different injury stages, there were significant differences in plasma metabolome. Progressing from T0 to T50 stages of injury, increased levels of neopterin, corticosterone, prostaglandin E2, tryptophan and testosterone, together with decreased levels of homocysteine, and estriol, were observed. Eventually, the quantitative prediction model of death warning was established. Cross-validation results showed that the predictive effect was good (RMSE=0.18408, R2=0.87 p=0.036).
Metabolomics approaches can be used to quantify the metabolic dynamics of patients with critically injuries and to predict death of critically injured patients by plasma 1H-NMR metabolomics.
本研究通过整合代谢组学技术与计算生物学方法,旨在探究重症创伤患者代谢动力学机制,并开发一种新的死亡早期预警方法。
开展前瞻性队列研究,收集重症创伤患者的分组血浆样本进行1H-NMR代谢组学分析。采用偏最小二乘回归对数据进行处理,以探究酶-基因网络调控机制在重症创伤代谢网络调控中的作用,并构建快速死亡预警的定量预测模型。
共纳入60例患者。存活患者与死亡患者的血浆代谢组存在显著差异。与存活患者相比,在死亡患者血浆中观察到112种调节新蝶呤、皮质酮、3-甲基组氨酸、同型半胱氨酸、丝氨酸、酪氨酸、前列腺素E2、色氨酸、睾酮和雌三醇这6种关键代谢标志物紊乱的酶和基因。在不同损伤阶段的患者中,血浆代谢组也存在显著差异。从损伤的T0期进展到T50期,新蝶呤、皮质酮、前列腺素E2、色氨酸和睾酮水平升高,同时同型半胱氨酸和雌三醇水平降低。最终,建立了死亡预警的定量预测模型。交叉验证结果表明预测效果良好(RMSE = 0.18408,R2 = 0.87,p = 0.036)。
代谢组学方法可用于量化重症创伤患者的代谢动力学,并通过血浆1H-NMR代谢组学预测重症创伤患者的死亡情况。