Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, No 45 Changchun Street, Xicheng District, Beijing, 100053, China.
China International Neuroscience Institute (China-INI), Xuanwu Hospital, Capital Medical University, Beijing, China.
J Neuroinflammation. 2022 Jun 22;19(1):165. doi: 10.1186/s12974-022-02522-x.
A major challenge in spinal dural arteriovenous fistula (SDAVF) is timely diagnosis, but no specific predictive biomarkers are known.
In the discovery cohort (case, n = 8 vs. control, n = 8), we used cerebrospinal fluid (CSF) and paired plasma samples to identify differentially expressed proteins by label-free quantitative proteomics. Further bioinformatics enrichment analyses were performed to screen target proteins. Finally, it was validated by ELISA in two of the new cohorts (case, n = 17 vs. control, n = 9), and univariate analysis, simple linear regression, and receiver operator characteristic (ROC) curve analysis were performed to evaluate the diagnostic potential.
In the discovery cohort, the most overexpressed proteins were APOB and C4BPA in CSF samples of patients. The GO/KEGG enrichment analysis indicated that the upregulated proteins were mainly involved in the acute inflammatory response and complement activation. Hub-gene analysis revealed that APP might be the key protein in the molecular interaction network. In the validation cohort, C4BPA and C1QA were significantly overexpressed in the CSF of patients, averaging 3046.9 ng/ml and 2167.2 ng/ml, respectively. Simple linear regression demonstrated that levels of C1QA and C4 were positively correlated with total protein in CSF (R = 0.8021, p = 0.0005; R = 0.7447, p = 0.0013). The areas under the ROC curves of C4BPA and C1QA were 0.86 and 1.00, respectively.
This study was the first to identify C4BPA and C1QA as potential biomarkers for the diagnosis of SDAVF and revealed that complement pathway activation might be one of the molecular mechanisms for venous hypertension myelopathy.
脊髓动静脉瘘（SDAVF）的主要挑战是及时诊断，但目前尚不知道具体的预测生物标志物。
在发现队列（病例，n=8 例 vs. 对照，n=8 例）中，我们使用脑脊液（CSF）和配对血浆样本通过无标记定量蛋白质组学来鉴定差异表达蛋白。进一步进行生物信息学富集分析以筛选靶蛋白。最后，在两个新队列中（病例，n=17 例 vs. 对照，n=9 例）通过 ELISA 进行验证，并进行单变量分析、简单线性回归和接收者操作特征（ROC）曲线分析，以评估诊断潜力。
在发现队列中，患者 CSF 样本中表达最上调的蛋白是 APOB 和 C4BPA。GO/KEGG 富集分析表明，上调蛋白主要涉及急性炎症反应和补体激活。枢纽基因分析表明，APP 可能是分子相互作用网络中的关键蛋白。在验证队列中，C4BPA 和 C1QA 在患者 CSF 中均显著过表达，平均分别为 3046.9ng/ml 和 2167.2ng/ml。简单线性回归表明，C1QA 和 C4 的水平与 CSF 中的总蛋白呈正相关（R=0.8021，p=0.0005；R=0.7447，p=0.0013）。C4BPA 和 C1QA 的 ROC 曲线下面积分别为 0.86 和 1.00。
本研究首次鉴定 C4BPA 和 C1QA 为 SDAVF 诊断的潜在生物标志物，并表明补体途径激活可能是静脉高压性脊髓病的分子机制之一。
Zotero 插件
