Sporadic Vestibular Schwannomas Associated With Good Hearing Secrete Higher Levels of Fibroblast Growth Factor 2 Than Those Associated With Poor Hearing Irrespective of Tumor Size

Abstract

We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. Fresh surgical specimens of VS were incubated in sterile PBS at 37°C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition ≥ 70% and pure-tone average ≤ 30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.