Subclinical diagnosis of cisplatin-induced ototoxicity with biomarkers.

Abstract

A mouse model with cisplatin-induced ototoxicity was used in addition to human samples from the ITMAT Biobank at the University of Pennsylvania. Mouse auditory brainstem responses (ABR), inner ear histology, perilymph cisplatin sampling, and measurement of serum prestin via ELISA were performed. Human serum prestin level was measured via ELISA in patients with otological issues after cisplatin treatment and compared to matched controls. Serum prestin was significantly elevated before ABR threshold shifts in mice exposed to cisplatin compared to control mice. Prestin concentration also correlated with the severity of hearing threshold shifts in mice. After an extended rest post-cisplatin treatment, prestin returned to baseline levels in mice and humans. Prestin was significantly elevated in the serum before the onset of objective hearing loss and correlated with the severity of hearing damage indicating that prestin may function as an effective biomarker of cisplatin-induced ototoxicity. Human serum prestin levels responded similarly to mice > 3 weeks from ototoxic exposure with decreased levels of prestin in the serum.