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 padj <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.