Ding Lu, Zhang Meiling, Fan Baochao, Deng Fuyuan, Li Zhenyuan, Han Yixuan, Wu Yifan, Zeng Jingchun, Lu Liming
Department of Traditional Chinese Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Neurol. 2025 Aug 8;16:1630390. doi: 10.3389/fneur.2025.1630390. eCollection 2025.
To systematically collate and evaluate metabolomics-based biomarkers of ischemic stroke (IS) to guide clinical diagnosis and treatment.
Comprehensive literature searches were conducted in PubMed, Embase, and Web of Science using "IS" and "metabolomics" as core keywords, covering publications up through February 2024. Any original metabolomic research related to IS was selected. Key information such as study demographics, study type, objectives, metabolomic analysis methods, and main findings were extracted and analyzed. Frequently mentioned metabolites were subjected to enrichment analysis using the MetaboAnalyst 6.0 platform.
A total of 51 studies were included. Quality assessment revealed that 54.8% of the diagnostic studies and 69.2% of the prognostic studies were high-quality, with most controlling for confounding factors. Metabolite analysis revealed associations between decreased proline, isoleucine, valine, and alanine levels with IS. Increased tyrosine, glutamine, phenylalanine, sphingomyelin, glutamate, lactate and glucose, and decreased LysoPC (18:2), histidine, and methionine levels were linked to IS onset. Specific metabolite combinations, such as serine, isoleucine, betaine, PC (5:0/5:0), and LysoPE (18:2), showed high precision in predicting acute ischemic stroke (AIS) (training set AUC = 0.988, test set AUC = 0.971). Glycine-serine-threonine and valine-leucine-isoleucine pathways were significant in diagnosing IS and AIS, and in differentiating ischemic and hemorrhagic strokes, as well as identifying post-stroke depression and cognitive impairment.
This study confirms the potential diagnostic and prognostic value of changes in amino acids and lipids, as well as other metabolites and metabolic pathways, in IS. These findings highlight the promise of metabolomics in IS diagnosis, differential diagnosis, risk assessment, and complication identification. However, further validation is needed due to the varying quality of the included studies.
https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42022335505.
系统整理和评估基于代谢组学的缺血性卒中（IS）生物标志物，以指导临床诊断和治疗。
以“IS”和“代谢组学”作为核心关键词，在PubMed、Embase和Web of Science数据库中进行全面文献检索，涵盖截至2024年2月的出版物。选取任何与IS相关的原始代谢组学研究。提取并分析研究人群、研究类型、目的、代谢组学分析方法和主要发现等关键信息。使用MetaboAnalyst 6.0平台对经常提及的代谢物进行富集分析。
共纳入51项研究。质量评估显示，54.8%的诊断性研究和69.2%的预后性研究为高质量研究，大多数研究控制了混杂因素。代谢物分析显示，脯氨酸、异亮氨酸、缬氨酸和丙氨酸水平降低与IS相关。酪氨酸、谷氨酰胺、苯丙氨酸、鞘磷脂、谷氨酸、乳酸和葡萄糖水平升高，以及溶血磷脂酰胆碱（18:2）、组氨酸和蛋氨酸水平降低与IS发病有关。特定的代谢物组合，如丝氨酸、异亮氨酸、甜菜碱、磷脂酰胆碱（5:0/5:0）和溶血磷脂酰乙醇胺（18:2），在预测急性缺血性卒中（AIS）方面显示出高精度（训练集AUC = 0.988，测试集AUC = 0.971）。甘氨酸 - 丝氨酸 - 苏氨酸和缬氨酸 - 亮氨酸 - 异亮氨酸途径在诊断IS和AIS、区分缺血性和出血性卒中以及识别卒中后抑郁和认知障碍方面具有重要意义。
本研究证实了氨基酸和脂质以及其他代谢物和代谢途径变化在IS中的潜在诊断和预后价值。这些发现凸显了代谢组学在IS诊断、鉴别诊断、风险评估和并发症识别方面的前景。然而，由于纳入研究质量参差不齐，需要进一步验证。
https://www.crd.york.ac.uk/PROSPERO/#myprospero，标识符CRD42022335505。
