蛋白质组学分析鉴定前庭神经鞘瘤患者血管通透性增加相关蛋白

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中文摘要

背景： 前庭神经鞘瘤（VS）是第VIII脑神经的良性肿瘤；占所有颅内肿瘤的6-8%，约占小脑脑桥角肿瘤的80%。囊性VS可能尤其危险，因其生长更快且术后结局更差。在本研究中，我们对来自实性和囊性VS患者的脑脊液（CSF）样本以及囊性VS患者的囊液进行了蛋白质组学分析。以面肌痉挛患者的CSF样本作为对照。方法：质谱（MS）分析在所有样本中鉴定出816种蛋白质，与对照组相比，VS患者样本中有111种蛋白质上调。上调的蛋白质属于补体系统成分和调节因子、与葡萄糖和脂质代谢相关的蛋白质类别。对囊性和实性VS患者CSF的MS分析鉴定出两个蛋白质组簇，富集于与神经系统发育、细胞黏附和髓鞘形成过程相关的蛋白质。结果：所获得的数据提示这些生物学过程参与囊性VS的发病机制。意义：本研究对实性和囊性前庭神经鞘瘤（VS）患者的脑脊液（CSF）和囊液进行了全面的蛋白质组学表征，为这些肿瘤的分子机制提供了有价值的见解。我们发现补体系统成分和调节因子在VS患者的CSF和囊液中持续上调，连同参与脂质代谢的蛋白质，提示血脑屏障破坏和囊肿形成的潜在机制，鉴于囊性VS更具侵袭性的临床病程，这一点尤其相关。这些发现不仅有助于理解VS的发病机制，还提示了未来诊断、预后和治疗策略的候选蛋白靶点，特别是针对更具挑战性的囊性形式疾病。结论：

英文摘要

Vestibular schwannomas (VS) are benign neoplasms of the VIII cranial nerve; they account for 6-8% of all intracranial tumors and about 80% of tumors of the cerebellopontine angle. Cystic forms of VS may be particularly dangerous, as they demonstrate faster growth and worse postoperative outcomes. In this study, we performed proteomic analysis of cerebrospinal fluid (CSF) samples obtained from patients with solid and cystic forms of VS, as well as cyst fluid from patients with cystic VS. CSF samples from patients with hemifacial spasm were used as controls. Mass spectrometric (MS) analysis resulted in identification of 816 proteins in all samples and 111 proteins were upregulated in samples obtained from VS patients compared to the control group. The upregulated proteins belonged to the groups of components and regulators of the complement system, proteins associated with glucose and lipid metabolism. MS analysis of CSF obtained from patients with cystic and solid forms of VS resulted in identification of two proteomic clusters enriched in proteins associated with the development of the nervous system, cell adhesion, and myelination processes. The data obtained suggest the involvement of these biological processes in the pathogenesis of cystic VS. SIGNIFICANCE: This study provides a comprehensive proteomic characterization of cerebrospinal fluid (CSF) and cyst fluid from patients with solid and cystic vestibular schwannomas (VS), offering valuable insights into the molecular mechanisms underlying these tumors. Our discovery that complement system components and regulators are consistently upregulated in CSF and cyst fluid from VS patients, along with proteins involved in lipid metabolism, points to a potential mechanism of blood-brain barrier disruption and cyst formation, which is particularly relevant given the more aggressive clinical course of cystic VS. These findings not only contribute to understanding of VS pathogenesis but also suggest candidate protein targets for future diagnostic, prognostic, and therapeutic strategies, particularly for the more challenging cystic form of the disease.