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首页> 外文期刊>International journal of molecular medicine >iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis
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iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis

机译：基于iTRAQ的脑脊液定量蛋白质组学分析显示NELL2是结核性脑膜炎的潜在诊断生物标志物

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Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. As TBM may result in permanent sequelae and death, rapid, accurate diagnostic tests using novel biomarkers are required for the early diagnosis and treatment of TBM. A quantitative proteomic study was therefore performed to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples were labelled with iTRAQ? and analyzed by LC?MS/MS. Gene ontology and Pathway analysis were conducted using DAVID bioinformatics resources. Neural epidermal growth factor?like like?2 (NELL2) with the largest fold?change value was selected for validation by western blotting. Proteomic phenotyping revealed over?representation in two inflammation?associated processes, complement and coagulation cascades as?well?as cell adhesion molecules. Western blotting showed a significant decrease in NELL2 levels in TBM subjects compared to healthy controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion, the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM. Further evaluation of these findings in larger studies including anti?tuberculosis medicated and unmedicated patient cohorts with other intracranial infectious diseases is required for clinical translation.
机译：结核性脑膜炎（TBM）是影响中枢神经系统的严重结核病并发症。由于TBM可能导致永久性后遗症和死亡，因此，对于TBM的早期诊断和治疗，需要使用新型生物标记物进行快速，准确的诊断测试。因此，进行了定量蛋白质组学研究，以鉴定从TBM患者（n = 12）和健康对照（n = 12）获得的脑脊液（CSF）中的差异蛋白。脑脊液样品用iTRAQ标记？并通过LC？MS / MS进行分析。使用DAVID生物信息学资源进行了基因本体论和通路分析。通过蛋白质印迹法选择具有最大倍数变化值的神经表皮生长因子，如α2（NELL2）。蛋白质组表型揭示了在两个与炎症相关的过程中的过度表达，补体和凝血级联以及细胞粘附分子。 Western印迹显示，与健康对照组相比，TBM受试者的NELL2水平显着降低。 AUC分析显示，NELL2能够以83.3％的敏感性和75％的特异性将TBM受试者与健康对照区分开。总之，结果表明，CSF NELL2是潜在的TBM诊断生物标志物。临床翻译需要在更大的研究中进一步评估这些发现，包括抗结核药物治疗和未药物治疗的人群以及其他颅内感染性疾病。

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