Tao Shuxin, Xiao Xinxing, Li Xin, Na Fan, Na Guo, Wang Shuang, Zhang Pin, Hao Fang, Zhao Peiran, Guo Dong, Liu Xuewu, Yang Dawei
Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
Department of Clinical Laboratory, Zibo Central Hospital, Zibo, Shandong, China.
Front Neurol. 2023 Apr 14;14:1153193. doi: 10.3389/fneur.2023.1153193. eCollection 2023.
The pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke.
We sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group).
It was found that upon comparing MB and MM to control patients, AAs shifts were detected partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924-0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966-1) which can be employed to effectively discriminate MM patients from control.
Overall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.
与急性缺血性中风（IS）相关的病理生理过程可反映在循环代谢组中。氨基酸（AAs）已被证明是中风后可发生显著改变的最重要代谢物之一。
我们试图使用一种广泛的靶向技术，基于超高效液相色谱串联质谱（UPLC-MS/MS）对27种不同的氨基酸进行可靠定量，以确定用于早期检测IS的潜在生物标志物。纳入了一个由216名参与者组成的队列，包括70名轻度至中度缺血性中风患者（美国国立卫生研究院卒中量表<15，MB组）、76名疑似中风患者（MM组）和70名健康对照者（NC组）。
通过偏最小二乘判别分析（PLS-DA）和通路分析发现，将MB组和MM组与对照患者进行比较时，检测到氨基酸变化。有趣的是，MB组和MM组表现出相似的氨基酸模式。此外，基于曲线下面积（AUC）为0.968（95%可信区间0.924-0.998），确定将鸟氨酸、天冬酰胺、缬氨酸、瓜氨酸和半胱氨酸纳入用于早期中风检测的生物标志物面板。在MB组中，鸟氨酸水平与梗死体积、3个月改良Rankin量表（mRS）评分及美国国立卫生研究院卒中量表（NIHSS）评分呈正相关。此外，一个包括鸟氨酸、牛磺酸、苯丙氨酸、瓜氨酸、半胱氨酸的代谢物生物标志物面板的AUC为0.99（95%可信区间0.966-1），可用于有效区分MM组患者与对照组。
总体而言，血清氨基酸变化是MB组和MM组的特征性代谢特征。由于本研究纳入了轻度至中度IS患者，氨基酸有望作为MB组患者早期诊断的生物标志物。氨基酸代谢可被视为IS预防和治疗的关键指标。
