High-throughput metabolite profiling: identification of plasma taurine as a potential biomarker of functional outcome after aneurysmal subarachnoid hemorrhage.
High-throughput metabolite profiling: identification of plasma taurine as a potential biomarker of functional outcome after aneurysmal subarachnoid hemorrhage.
复制标题
高通量代谢物分析：鉴定血浆牛磺酸作为动脉瘤性蛛网膜下腔出血后功能结果的潜在生物标志物。
作者：
C. Stapleton;A. Acharjee;Hannah J Irvine;Zoe Wolcott;A. Patel;W. Kimberly
目标
代谢分析（或代谢组学）可以识别疾病的候选生物标志物，并有可能发现新的干预途径。本研究的目的是确定蛛网膜下腔出血（SAH）后功能结果的潜在生物标志物。
方法
作者对 2011 年 5 月至 2016 年 10 月期间就诊于马萨诸塞州总医院的 191 名 SAH 患者的血浆样本进行了多种化学类别（163 种代谢物）的高通量代谢物分析。在发作后的 3 个时间点抽取样本：0-5 天、6-10 天和 11-14 天。进行弹性网 (EN) 和 LASSO（最小绝对收缩和选择算子）机器学习分析，以确定与 90 天功能结果相关的代谢物，并通过修改后的 Rankin 量表 (mRS) 进行评估。然后进行额外的单变量和多变量分析，以进一步检查代谢物与临床变量和 90 天功能结果之间的关系。
结果
137 名（71.7%）动脉瘤性 SAH 患者符合纳入标准。 79 名 (57.7%) 患者在 90 天时获得了良好的功能结果（mRS 评分 0-2）。预后良好的患者年龄较小（p = 0.002），入院时 Hunt 和 Hess 分级（p < 0.0001）和改良 Fisher 分级（p < 0.0001）较低，并且未出现脑积水（p < 0.0001）或迟发性脑缺血（DCI）（p = 0.049）。 EN 和 LASSO 机器学习方法将牛磺酸确定为与 90 天功能结果相关的主要代谢物 (p < 0.0001)。动脉瘤性蛛网膜下腔出血后第 0 天和第 5 天收集的样本中，氨基酸牛磺酸的血浆浓度在预后良好的患者中比预后差的患者高出 21.9% (p = 0.002)。 Logistic 回归表明，在调整年龄、Hunt 和 Hess 分级、改良 Fisher 分级、脑积水和 DCI 后，牛磺酸仍然是功能结果的重要预测因子（p = 0.013；OR 3.41，95% CI 1.28-11.4）。
结论
动脉瘤性蛛网膜下腔出血后血浆牛磺酸水平升高预示着良好的 90 天功能结果。虽然动物实验证据表明这种效应可能是通过促炎细胞因子的下调介导的，但还需要更多的研究来验证人类的这一假设。
OBJECTIVE
Metabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).
METHODS
The authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0-5, 6-10, and 11-14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.
RESULTS
One hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0-2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28-11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.
CONCLUSIONS
Elevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.
影响因子：
8
作者：
Kimberly, W. Taylor;O'Sullivan, John F.;Gerszten, Robert E.
通讯作者：
Gerszten, Robert E.
影响因子：
9.3
作者：
Rhee EP;Gerszten RE
通讯作者：
Gerszten RE
影响因子：
15.9
作者：
Lewis, Gregory D.;Wei, Ru;Gerszten, Robert E.
通讯作者：
Gerszten, Robert E.