Neurosurgery Center, Department of Cerebrovascular Surgery, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China. Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, 510280, Guangdong, China.; Department of cerebrovascular surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No 600 Tianhe Road, Guangzhou 510630, Guangdong, China.
Department of cerebrovascular surgery, The Third Affiliated Hospital of Sun Yat-Sen University, No 600 Tianhe Road, Guangzhou 510630, Guangdong, China; Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
J Proteomics. 2023 Mar 20;275:104820. doi: 10.1016/j.jprot.2023.104820. Epub 2023 Jan 13.
CVST is a type of venous stroke that mainly affects young adults with no reliable diagnostic markers and effective treatment strategies for secondary pathologies. However, the underlying pathological molecular mechanisms remain unclear. Here, we systematically analyzed the molecule profiling of the cerebrospinal fluid (CSF) in CVST patients via tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for the diagnosis and treatment of CVST. Five CVST patients and five control patients were selected, and CSF samples were analyzed by TMT proteomics. Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Besides, parallel reaction monitoring (PRM) was utilized to validate the DEPs. 468 differentially expressed proteins were screened, 185 of which were up-regulated and 283 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis displayed that these proteins were significantly enriched in multiple pathways related to a variety of pathophysiological processes. PRM verification showed that apolipoprotein E, MMP-2, neuroserpin, clusterin, and several other molecules were down-regulated. These identified proteins reveal unique pathophysiological characteristics secondary to CVST. Further characterization of these proteins in future research could enable their application as potential therapeutic targets and biomarkers in CVST therapy. SIGNIFICANCE: Cerebral venous sinus thrombosis (CVST) is an underrated and potentially fatal cause of stroke with a reported mortality of 5-10% worldwide. Currently, in addition to anticoagulant and thrombolytic therapy, effective treatments targeting the injured brain parenchyma after CVST remain limited. Besides, accurate diagnostic markers are still sorely lacking. In the present study, we will detect the alterations of the CSF protein spectrum of CVST patients by TMT technique, screen differentially expressed proteins, analyze the functions of these signals through bioinformatics methods, and finally validate the key molecules through parallel reaction monitoring (PRM) technique. Collectively, the study aimed to offer a reference for the discovery of specific protein/pathway alterations in the CSF of CVST patients and further reveal the underlying pathogenesis, thereby providing evidence for the diagnosis and treatment of CVST.
颅内静脉窦血栓形成（CVST）是一种被低估的、潜在致命性的卒中类型，全球范围内的死亡率为 5-10%。目前，除了抗凝和溶栓治疗外，针对 CVST 后受损脑实质的有效治疗方法仍然有限。此外，准确的诊断标志物仍然严重缺乏。在本研究中，我们将通过 TMT 技术检测 CVST 患者 CSF 蛋白谱的变化，筛选差异表达蛋白，通过生物信息学方法分析这些信号的功能，最后通过平行反应监测（PRM）技术验证关键分子。总的来说，该研究旨在为发现 CVST 患者 CSF 中特定蛋白/通路的改变提供参考，并进一步揭示潜在的发病机制，从而为 CVST 的诊断和治疗提供依据。
