Department of Neurology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, USA.
Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, USA.
J Stroke Cerebrovasc Dis. 2022 Apr;31(4):106320. doi: 10.1016/j.jstrokecerebrovasdis.2022.106320. Epub 2022 Jan 29.
Stroke is a major cause of serious disability in the United States. Previous studies found multiple associations of serum metabolites with acute ischemic stroke (AIS) compared to controls, but few of them evaluated metabolome in a longitudinal fashion. Therefore, we compared the metabolome of the acute and chronic stages of ischemic stroke.
We evaluated 1295 serum metabolites from the cohort of 60 stroke patients at acute and chronic stages by performing global metabolomics using ultra-high-performance liquid chromatography/mass spectrometry (LC-MS) and gas chromatography/mass spectrometry (GC-MS). We used Orthogonal Partial Least Square-Discrimination Analysis (OPLS-DA) to inspect group disparity and a mixed regression model to compare metabolites in the acute and chronic stages with Two-Stage Benjamini & Hochberg (TSBH) and Bonferroni correction for multiple testing.
The OPLS-DA revealed significant separation of acute and chronic stage metabolites. Mixed regression identified 228 metabolites with TSBH, and 29 metabolites with Bonferroni correction different in acute and chronic stages. At the acute stage, there was a consistent increase of the metabolites of mono/diacylglycerols, sphingolipids, medium/long-chain fatty acids, and amino acids glycine, valine, and tyrosine. At the same time, there was a consistent decrease of the metabolites of acyl-choline related fatty acids, phospholipids, and amino acids alanine, aspartate, and tyramine. Additionally, we identified eight novel metabolites significantly altered at the acute stage of stroke.
Our pilot study demonstrated significant alterations in metabolomic patterns between the acute and chronic stages of stroke, validating some case-control findings. Future investigation in a larger independent cohort is warranted to identify early biomarkers of acute ischemic stroke.
在美国，中风是导致严重残疾的主要原因。与对照组相比，先前的研究发现了多种血清代谢物与急性缺血性中风（AIS）之间的关联，但很少有研究从纵向角度评估代谢组。因此，我们比较了缺血性中风急、慢性期的代谢组。
我们通过超高效液相色谱/质谱联用（LC-MS）和气相色谱/质谱联用（GC-MS）对 60 例中风患者急性和慢性期的 1295 种血清代谢物进行了全局代谢组学评估。我们使用正交偏最小二乘判别分析（OPLS-DA）检查组间差异，并使用混合回归模型比较急性和慢性期的代谢物，采用 Two-Stage Benjamini & Hochberg（TSBH）和 Bonferroni 校正进行多重检验。
OPLS-DA 显示出急性和慢性期代谢物的显著分离。混合回归确定了 228 个 TSBH 代谢物，29 个 Bonferroni 校正代谢物在急性和慢性期不同。在急性期，单/二酰甘油、鞘脂、中/长链脂肪酸和氨基酸甘氨酸、缬氨酸和酪氨酸的代谢物持续增加。与此同时，酰胆碱相关脂肪酸、磷脂和氨基酸丙氨酸、天冬氨酸和酪胺的代谢物持续减少。此外，我们还鉴定出 8 种在中风急性期明显改变的新型代谢物。
我们的初步研究表明，中风急、慢性期的代谢组模式存在显著差异，验证了一些病例对照研究的结果。需要在更大的独立队列中进行进一步研究，以确定急性缺血性中风的早期生物标志物。
