Biomarkers in Vestibular Schwannoma-Associated Hearing Loss.

Luis Lassaletta,Jose Manuel Morales-Puebla,Victor Martinez-Glez,Pablo Lapunzina,Miryam Calvino,Lourdes Rodriguez-De La Rosa,Isabel Varela-Nieto

doi:10.3389/fneur.2019.00978

Abstract

Vestibular schwannomas (VSs) are benign tumors composed of differentiated neoplastic Schwann cells. They can be classified into two groups: sporadic VS and those associated with neurofibromatosis type 2 (NF2). VSs usually grow slowly, initially causing unilateral sensorineural hearing loss (HL) and tinnitus. These tumors cause HL both due to compression of the auditory nerve or the labyrinthine artery and due to the secretion of different substances potentially toxic to the inner ear or the cochlear nerve. As more and more patients are diagnosed and need to be managed, we are more than ever in need of searching for biomarkers associated with these tumors. Owing to an unknown toxic substance generated by the tumor, HL in VS may be linked to a high protein amount of perilymph. Previous studies have identified perilymph proteins correlated with tumor-associated HL, including μ-Crystallin (CRYM), low density lipoprotein receptor-related protein 2 (LRP2), immunoglobulin (Ig) γ-4 chain C region, Ig κ-chain C region, complement C3, and immunoglobulin heavy constant γ 3. Besides, the presence of specific subtypes of heat shock protein 70 has been suggested to be associated with preservation of residual hearing. It has been recently demonstrated that chemokine receptor-4 (CXCR4) is overexpressed in sporadic VS as well as in NF2 tumors and that hearing disability and CXCR4 expression may be correlated. Further, the genetic profile of VS and its relationship with poor hearing has also been studied, including DNA methylation, deregulated genes, growth factors, and NF2 gene mutations. The knowledge of biomarkers associated with VS would be of significant value to maximize outcomes of hearing preservation in these patients.

Highlights

Vestibular schwannomas (VSs), previously termed acoustic neuromas, are non-malignant tumors composed of Schwann cells of the vestibulocochlear nerve (VIII cranial nerve), arising from either the internal auditory canal (IAC) or the cerebellopontine angle (CPA)
Several markers such as perilymph proteins have been associated with tumor hearing loss
Specific subtypes of HSP70 have been correlated with hearing outcomes

Summary

INTRODUCTION

Vestibular schwannomas (VSs), previously termed acoustic neuromas, are non-malignant tumors composed of Schwann cells of the vestibulocochlear nerve (VIII cranial nerve), arising from either the internal auditory canal (IAC) or the cerebellopontine angle (CPA). They can be classified into two groups: sporadic VS and those associated with neurofibromatosis type 2 (NF2) [1]. Diagnosis of VS may be either from cranial MRI performed for unrelated complaints or, usually, due to unilateral hearing loss or tinnitus [1, 9]. As more and more patients are diagnosed and need to be managed, we are more than ever in need of searching for biomarkers associated with these tumors, in order to help with the choice of selecting between a “wait-and-scan” approach and surgery [15] aimed at reducing morbidity and increasing the hearing outcomes [4]

BIOLOGICAL MARKERS

Perilymph Proteome

Tissue Sample Proteins

Molecular Biology

Findings

CONCLUSION