Schmitt Heike A, Pich Andreas, Schröder Anke, Scheper Verena, Lilli Giorgio, Reuter Günter, Lenarz Thomas
Department of Otolaryngology, Hannover Medical School , Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Cluster of Excellence of the German Research Foundation (DFG; "Deutsche Forschungsgemeinschaft") "Hearing4all", Hannover Medical School , Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
J Proteome Res. 2017 May 5;16(5):1911-1923. doi: 10.1021/acs.jproteome.6b00986. Epub 2017 Apr 13.
The knowledge about the etiology and pathophysiology of sensorineural hearing loss (SNHL) is still very limited. This study aims at the improvement of understanding different types of SNHL by proteome analysis of human perilymph. Sampling of perilymph was established during inner ear surgeries (cochlear implantation, vestibular schwannoma surgeries), and safety of the sampling method was determined by checking hearing threshold with pure-tone audiometry postoperatively. An in-depth shot-gun proteomics approach was performed to identify cochlear proteins and the individual proteome in perilymph of patients. This method enables the identification and quantification of protein composition of perilymph. The proteome of 41 collected perilymph samples with volumes of 1-12 μL was analyzed by data-dependent acquisition, resulting in overall 878 detected protein groups. At least 203 protein groups were solely identified in perilymph, not in reference samples (serum, cerebrospinal fluid), displaying a specific protein pattern for perilymph. Samples were grouped by patient's age and surgery type, leading to the identification of some proteins specific to particular subgroups. Proteins with different abundances between different sample groups were subjected to classification by gene ontology annotations. The identified proteins might serve as biomarkers to develop tools for noninvasive inner ear diagnostics and to elucidate molecular profiles of SNHL.
关于感音神经性听力损失（SNHL）的病因和病理生理学的知识仍然非常有限。本研究旨在通过对人外淋巴进行蛋白质组分析来增进对不同类型SNHL的理解。在内耳手术（人工耳蜗植入、前庭神经鞘瘤手术）期间建立了外淋巴采样，并通过术后纯音听力测定检查听力阈值来确定采样方法的安全性。采用深度鸟枪法蛋白质组学方法来鉴定耳蜗蛋白和患者外淋巴中的个体蛋白质组。这种方法能够鉴定和定量外淋巴的蛋白质组成。通过数据依赖型采集分析了41份体积为1 - 12μL的收集到的外淋巴样本的蛋白质组，共检测到878个蛋白质组。至少有203个蛋白质组仅在外淋巴中被鉴定出来，而在参考样本（血清、脑脊液）中未被鉴定，显示出外淋巴特有的蛋白质模式。样本按患者年龄和手术类型分组，从而鉴定出一些特定亚组特有的蛋白质。对不同样本组间丰度不同的蛋白质进行基因本体注释分类。所鉴定出的蛋白质可能作为生物标志物，用于开发非侵入性内耳诊断工具并阐明SNHL的分子特征。
