Abstract
Objectives: 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.Methods: The venous blood samples of 94 ischemic stroke patients and 35 brain tumor-stroke mimics (BT-SM) 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.Results: Median ratio of total TF-UP/LRP was 0.85 (Interquartile range, 0.21) in the brain tumor-stroke mimics (BT-SM) group, and 0.45 (0.14) in the ischemic stroke group; median Alb-UP/LRP ratio was 0.66 (0.16) in the BT-SM 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 (P < 0.0001), but not for Alb-UP/LRP (P = 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, P < 0.0001).Conclusions: 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.
Highlights
Oxidative stress plays an important role in neuronal injuries and free iron is responsible for oxidative damage in the infarcted brain tissues [1,2,3,4]
Ding et al reported that the expression of ferritin and TF receptors (TFR) was increased in the ischemic cerebral cortex and hippocampus, but the expression of ferroprotein 1, an iron-export protein, and hepcidin, the key regulator of ferroprotein 1, was significantly decreased in infarcted brain tissues [11]
The prevalence of diabetes mellitus or hypertension was significantly higher in the ischemic stroke group (Table 1)
Summary
Oxidative stress plays an important role in neuronal injuries and free iron is responsible for oxidative damage in the infarcted brain tissues [1,2,3,4]. Ding et al reported that the expression of ferritin and TFR was increased in the ischemic cerebral cortex and hippocampus, but the expression of ferroprotein 1, an iron-export protein, and hepcidin, the key regulator of ferroprotein 1, was significantly decreased in infarcted brain tissues [11]. In a case-control study, lower level of TF and higher level of ferritin were found in the serum of 42 stroke patients, compared with 62 healthy controls [2]. All these observations suggest that TF is involved in the brain tissue infarction. To our knowledge, the correlation between serum TF level and the probability of acute ischemic stroke has not been studied before
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