Yu Yan, Liu Peijia, Liu Yang, Zhang Zhaobo, Kong Xiaotong, Wang Ning, Sun Xuesong, Xu Chen, Bai Xue, Su Wanling, Cao Ying, Zou Xingbang, Luo Doudou, Huang Yin, Liu Peifang
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Sci Rep. 2025 Jul 2;15(1):23574. doi: 10.1038/s41598-025-09375-3.
Acute ischemic stroke (AIS) subtypes exhibit distinct pathophysiological mechanisms. While current classification methods predominantly depend on neuroimaging, there remains a critical need for sensitive biomarkers to complement imaging and enhance early subtype identification in clinical settings. This study employed metabolomics to identify such biomarkers. A total of 320 AIS patients within 48 h of symptom onset were enrolled, including 227 with large artery atherosclerosis (LAA) and 93 with small vessel occlusion (SVO). Participants were divided into a discovery cohort (n = 177) and a validation cohort (n = 143) based on enrollment order. Pseudotargeted serum metabolomic profiling was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Distinct metabolomic signatures were observed between LAA and SVO subtypes. Three differentiating metabolites-glycoursodeoxycholic acid, docosapentaenoic acid (22n-6), and FAHFA 38:4-were consistently identified and validated across both cohorts. Combined analysis of these metabolites significantly enhanced the discriminatory power for AIS subtype differentiation. This study presents these three circulating metabolites that have the potential to serve as novel biomarkers for the early differentiation between LAA and SVO subtypes of AIS.
急性缺血性卒中（AIS）亚型具有不同的病理生理机制。虽然目前的分类方法主要依赖于神经影像学，但仍然迫切需要敏感的生物标志物来补充影像学检查，并在临床环境中加强早期亚型识别。本研究采用代谢组学来识别此类生物标志物。共纳入320例症状发作48小时内的AIS患者，其中227例为大动脉粥样硬化（LAA）型，93例为小血管闭塞（SVO）型。根据入组顺序将参与者分为发现队列（n = 177）和验证队列（n = 143）。使用液相色谱-串联质谱（LC-MS/MS）进行伪靶向血清代谢组学分析。在LAA和SVO亚型之间观察到不同的代谢组学特征。在两个队列中一致鉴定并验证了三种具有鉴别作用的代谢物——甘氨鹅去氧胆酸、二十二碳五烯酸（22n-6）和脂肪酸酯酰胺38:4。这些代谢物的联合分析显著增强了AIS亚型鉴别的区分能力。本研究提出了这三种循环代谢物，它们有可能作为AIS的LAA和SVO亚型早期区分的新型生物标志物。
