Proteomic Analysis Identifies Novel Plasma Biomarkers in Patients With Vestibular Schwannoma

Hypothesis: Patients with sporadic vestibular schwannoma (VS) have unique plasma protein biomarkers that distinguish them from patients without VS. Background: No reliable molecular biomarker of VS exists. MRI biomarkers offer limited insight into VS pathophysiology. Identification of plasma biomarkers could enhance disease prognostication and guide treatment decisions. Methods: A high-throughput DNA aptamer-based proteomic analysis was performed in plasma samples from 12 individuals, 6 with sporadic, non-irradiated and growing VS and 6 age-matched and sex-matched healthy controls (HCs). Dysregulated proteins were identified using a cutoff value of |log 2 foldchange|>1 and p adj <0.05. Enriched pathways were determined using Ingenuity Pathway and STRING bioinformatic analysis. Biomarker expression was validated in an established human schwannoma cell line and primary VS culture. Results: A total of 7310 proteins were profiled. Of 1499 differentially expressed proteins, 152 (10%) were upregulated and 264 (18%) were downregulated in VS. There was an enrichment in cancer proliferation, protein catabolism, and immune cell activation processes. A panel of 40 proteins distinguished VS from HC, accounting for 84% of the variance on principal component analysis. These included members of NF-κB and Wnt signaling pathways (NFKBIA, WNT10A, and WNT16). IGFBP-2 and FCGR3A mRNA expression were significantly elevated in schwannoma cells. Hepcidin (HAMP), a regulator of iron homeostasis that influences tumor growth, was highly expressed in human VS tissue and enriched in primary VS culture secretion. Conclusions: Proteomic analysis of VS patient plasma identified several disease-classifying biomarkers. Hepcidin warrants further investigation into its role in VS progression.