Proteomic analysis identifies proteins involved in increased vascular permeability in vestibular schwannoma patients

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.