Hu Xizheng, Li Yinghui, Cheng Peng, Wu Anhua, Li Guangyu
Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
Department of Medical Genetics, School of Life Science, China Medical University, Shenyang, China.
Front Neurol. 2021 Feb 5;12:619310. doi: 10.3389/fneur.2021.619310. eCollection 2021.
Free irons are transported into brain tissues by transferrin and play an important role in neuronal/glial cell damage. Lower serum levels of transferrin have been found in patients with ischemic stroke, compared with healthy subjects. In present study, we investigated whether transferrin unique peptide (TF-UP) could be employed as a serum biomarker for brain tissue damage in acute ischemic stroke. The venous blood samples of 94 ischemic stroke patients and 35 patients were collected within the first 72 h (Median time 23.25, Interquartile range 60.75) of acute onset in the emergency room. Total TF-UP and total albumin unique peptide (Alb-UP) were identified with liquid chromatography/mass spectrometry (LC-MS/MS) and quantified by multiple reaction monitoring (MRM) method using labeled reference peptide (LRP) for further analysis. Median ratio of total TF-UP/LRP was 0.85 (Interquartile range, 0.21) in the group, and 0.45 (0.14) in the ischemic stroke group; median Alb-UP/LRP ratio was 0.66 (0.16) in the group, and 0.55 (0.20) in the ischemic stroke group. The overall trend from low to high levels was statistically significant for TF-UP/LRP ( < 0.0001), but not for Alb-UP/LRP ( = 0.1667). According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9565 and the optimal cutoff value of serum TF-UP was 0.6317, which yielded a sensitivity of 91.49% and a specificity of 88.57%. The odds ratio (95% confidence intervals) of serum TF-UP/LRP was 83.31 (23.43, 296.22, < 0.0001). Serum TF-UP/LRP level is decreased in patients with acute ischemic stroke in comparison with brain tumor, and it may serve as a serum biomarker for the neuronal/glial cell damage in cerebral infarction.
游离铁通过转铁蛋白转运至脑组织中,并在神经元/胶质细胞损伤中发挥重要作用。与健康受试者相比,缺血性中风患者的血清转铁蛋白水平较低。在本研究中,我们调查了转铁蛋白独特肽(TF-UP)是否可作为急性缺血性中风脑组织损伤的血清生物标志物。在急诊室急性发病的前72小时内(中位时间23.25,四分位间距60.75)收集了94例缺血性中风患者和35例对照患者的静脉血样本。采用液相色谱/质谱联用(LC-MS/MS)鉴定总TF-UP和总白蛋白独特肽(Alb-UP),并使用标记参考肽(LRP)通过多反应监测(MRM)方法进行定量,以进行进一步分析。对照组中总TF-UP/LRP的中位数比值为0.85(四分位间距,0.21),缺血性中风组为0.45(0.14);对照组中Alb-UP/LRP的中位数比值为0.66(0.16),缺血性中风组为0.55(0.20)。TF-UP/LRP从低水平到高水平的总体趋势具有统计学意义(P<0.0001),但Alb-UP/LRP则无统计学意义(P = 0.1667)。根据受试者工作特征(ROC)曲线,曲线下面积(AUC)为0.9565,血清TF-UP的最佳截断值为0.6317,灵敏度为91.49%,特异性为88.57%。血清TF-UP/LRP的比值比(95%置信区间)为83.31(23.43,296.22,P<0.0001)。与脑肿瘤患者相比,急性缺血性中风患者的血清TF-UP/LRP水平降低,它可能作为脑梗死中神经元/胶质细胞损伤的血清生物标志物。