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Proteomic Analysis Identifies Novel Plasma Biomarkers in Patients With Vestibular Schwannoma.

Proteomic Analysis Identifies Novel Plasma Biomarkers in Patients With Vestibular Schwannoma. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Nguyen, H. T., Kuo, H., Vasilijic, S., Giordano, G., Libermann, T., Stankovic, K. M., Ren, Y. 2025

Abstract

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 |log2foldchange|>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-kappaB 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.

View details for DOI 10.1097/MAO.0000000000004729

View details for PubMedID 41249026