Vasilijic Sasa, Atai Nadia A, Hyakusoku Hiroshi, Worthington Steven, Ren Yin, Sagers Jessica E, Sahin Mehmet I, Fujita Takeshi, Landegger Lukas D, Lewis Richard, Welling D Bradley, Stankovic Konstantina M
Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA, US.
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, US.
bioRxiv. 2023 Jan 26:2023.01.24.525436. doi: 10.1101/2023.01.24.525436.
Vestibular schwannoma (VS) is intracranial tumor arising from neoplastic Schwann cells, causing hearing loss in about 95% of patients. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. Here, we conducted profiling of patients' plasma for 67 immune-related factors on a large cohort of VS patients (N>120) and identified candidate biomarkers associated with tumor growth (IL-16 and S100B) and hearing (MDC). We identified the 7-biomarker panel composed of MCP-3, BLC, S100B, FGF-2, MMP-14, eotaxin, and TWEAK that showed outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS-induced hearing loss and provided a unique diagnostic tool that may predict hearing change and tumor growth in VS patients and may help inform the ideal timing of tumor resection to preserve hearing.
前庭神经鞘瘤(VS)是一种起源于肿瘤性施万细胞的颅内肿瘤,约95%的患者会出现听力丧失。传统观点认为听力缺陷是由VS的物理扩张压迫听神经所致,但这无法解释临床上常见的现象,即小肿瘤患者也可能有严重听力丧失,这表明肿瘤分泌的因子可能影响VS患者的听力。在此,我们对一大群VS患者(N>120)的血浆进行了67种免疫相关因子的分析,并确定了与肿瘤生长(IL-16和S100B)和听力(MDC)相关的候选生物标志物。我们确定了由MCP-3、BLC、S100B、FGF-2、MMP-14、嗜酸性粒细胞趋化因子和TWEAK组成的7种生物标志物组合,该组合对VS具有出色的鉴别能力。这些发现揭示了VS所致听力丧失可能的治疗靶点,并提供了一种独特的诊断工具,可预测VS患者的听力变化和肿瘤生长,还可能有助于确定保留听力的肿瘤切除理想时机。