Protein profiling of cerebrospinal fluid from patients undergoing vestibular schwannoma surgery and clinical significance

Abstract Vestibular schwannoma (VS) is a common disease in the region of the cerebellopontine angle in the posterior cranial fossa. Large VS and its surgical management usually lead to severe cranial nerve dysfunction and affect the patient’s quality of life. We aimed to find some possible progression markers of VS. Here, we sought to characterize the cerebrospinal fluid (CSF) proteome of patients with different VS grades and recurrence to identify biomarkers predictive of VS growth or recurrence. CSF was collected intraoperatively prior to removal of untreated VS, including grade I–V and recurrence. Isobaric tags for relative and absolute quantitation–based proteomic analysis of CSF from 43 VS patients and 3 control patients was used to identify candidate proteins. Ninety-three overlapping proteins were found to display differential expression in grade I, II, III, IV, and V VS patients compared with the control group. Nine proteins were chosen for validation with enzyme-linked immunosorbent assay. VS was distinguished from control patients based on the expression patterns of six proteins (ATP-binding cassette subfamily A member 3 [ABCA3], secretogranin-1 [SCG1], Krueppel-like factor 11 [KLF11], voltage-dependent calcium channel subunit alpha-2/delta-1 [CA2D1], brain acid soluble protein 1 [BASP1], and peroxiredoxin-2 [PRDX2]. ABCA3 and KLF11 were positively correlated with the size of early-phase of VS, while BASP1 and PRDX2 showed a negative correlation. ABCA3, CA2D1, and KLF11 were upregulated, while BASP1 and PRDX2 were downregulated in the CSF from VS recurrence. But SCG1 was increased only at early-phase. These data suggest that increased ABCA3 and KLF11 and decreased BASP1 and PRDX2 in CSF are associated with VS growth at the early phase or recurrence.