Abstract
Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies.
Highlights
Computational biomedicine integrating clinical and omics data is a modern and powerful approach for the development of novel, molecular and individualized diagnosis and treatment regimen
Cochlear implant recipients (n = 75 implanted ears), who were previously analysed in regard to the proteome profiles of their perilymph, were used for retrospective analysis of clinical data on hearing performance and speech intelligibility one year after cochlear implant surgery
The results of audiological speech intelligibility one year after cochlear implantation were available for 45 of the 68 patients. These patients were divided into two groups according to their performance data (Fig 1): Patients with good performance (n = 22) were defined with HSM sentence test in noise 10 dB > 30% and Freiburg monosyllables test > 65%, those with poor performance (n = 14) were defined with HSM sentence test in noise 10 dB < 30% and Freiburg monosyllables test < 65%
Summary
Computational biomedicine integrating clinical and omics data is a modern and powerful approach for the development of novel, molecular and individualized diagnosis and treatment regimen. When the inner ear is affected from disease, both organ functions, i.e., hearing and balance, rapidly deteriorate and in many cases do not recover. State of the art treatment of hearing loss is cochlear implantation, the insertion of an electrode array into the cochlea for direct electrical activation of the auditory nerve [3]. With this approach, the damaged sensory epithelium of the cochlea, which is responsible for translating sound into electrical signals, is bypassed
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