Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics

Shuxin Tao; Xinxing Xiao; Xin Li; Fan Na; Guo Na; Shuang Wang; Pin Zhang; Fang Hao; Peiran Zhao; Dong Guo; Xuewu Liu; Dawei Yang

doi:10.3389/fneur.2023.1153193

Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics

Front Neurol. 2023 Apr 14:14:1153193. doi: 10.3389/fneur.2023.1153193. eCollection 2023.

Authors

Shuxin Tao¹, Xinxing Xiao¹, Xin Li², Fan Na³, Guo Na⁴, Shuang Wang³, Pin Zhang⁴, Fang Hao¹, Peiran Zhao³, Dong Guo¹, Xuewu Liu⁵, Dawei Yang³

Affiliations

¹ Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
² Department of Clinical Laboratory, Zibo Central Hospital, Zibo, Shandong, China.
³ Zhong Yuan Academy of Biological Medicine, Liaocheng People's Hospital, Liaocheng, China.
⁴ Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
⁵ Department of Neurology, Qilu Hospital of Shandong University, Institute of Epilepsy, Shandong University, Jinan, Shandong, China.

Abstract

Background: 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.

Methods: 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).

Results: It was found that upon comparing MB and MM to control patients, AAs shifts were detected via 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.

Conclusion: 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.

Keywords: amino acids; biomarker; ischemic stroke; stroke mimics; targeted metabolomics.