Proteome profile of patients with excellent and poor speech intelligibility after cochlear implantation: Can perilymph proteins predict performance?

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.

Hearing loss and its association with the proteome of perilymph, cerebrospinal fluid, and tumor tissue in patients with vestibular schwannoma

“…Upregulation of IGHV1-2, IGHV1-46, and IGKV6-21, indicating B-cell involvement, is reported to be associated with poor hearing performance. In contrast, IGKV4-1 and Complement C8 upregulation has been shown to be associated with excellent hearing performance one year after cochlear implantation 16 . Complement C8 contributes to the membrane attack complex binding to C5b 59 and cell lysis 32 .…”

“…Since the first mass spectroscopy-based proteome study in 2011 12 , the human perilymph proteome has been further explored in a series of studies on samples obtained during surgery 13 , 16 , 17 , 29 . While the number of patients in each study has been limited, the results have improved knowledge of the PL proteome profile and its function under normal and pathological conditions.…”

Electrochemical Degradation of Molecularly Imprinted Polymers for Future Applications of Inflammation Sensing in Cochlear Implants

“…Therefore, information about inflammation is crucial for the timely administration of anti-inflammatory medication or to facilitate surgical planning. There are currently different research approaches that target the detection of inflammation e.g., perilymph analysis during CI surgery. , Since inflammation can occur up to 6 weeks after surgery, the accuracy of such analysis is limited. Therefore, molecularly imprinted polymers (MIPs) have been proposed as sensors for timely inflammation marker detection in body fluids on CI, as it is possible to deposit MIPs on the CI electrode. − Since MIP sensors for implants would remain in the body for years, high standards must be fulfilled with regard to biocompatibility.…”

“…There are currently different research approaches that target the detection of inflammation e.g., perilymph analysis during CI surgery. 6 , 7 Since inflammation can occur up to 6 weeks after surgery, the accuracy of such analysis is limited. Therefore, molecularly imprinted polymers (MIPs) have been proposed as sensors for timely inflammation marker detection in body fluids on CI, as it is possible to deposit MIPs on the CI electrode.…”

Dual viscosity mixture vehicle for intratympanic steroid treatment modifies the ROS and inflammation related proteomes

“…The cochlea is covered with thick bone, and the inner ear compartment is isolated from other parts of the body by the blood labyrinthine barrier (LBL). Only a handful of studies have been able to access inner ear fluid for in-depth proteomic analysis ( Szeto et al, 2021 ; Durisin et al, 2022 ; van Dieken et al, 2022 ).…”