Experimental validation and identification of ferroptosis-associated biomarkers for diagnostic and therapeutic targeting in hearing loss.

OBJECTIVES

Ferroptosis, a regulated form of cell death, has attracted significant attention in hearing loss research; however, the role of ferroptosis-related genes remains unclear. This study aimed to clarify diagnostic and therapeutic targeting of ferroptosis-related genes in hearing loss.

METHODS

Differentially expressed genes related to hearing loss from the GEO database were intersected with ferroptosis-related genes. The Lasso and SVM-RFE models were applied to reduce the gene set, identifying model genes. Biological functions, pathways, and gene-drug associations related to these model genes were analyzed. Age-related hearing loss (ARHL) genes within the model genes were obtained from a genome-wide association study (GWAS) dataset. Further validation was conducted in HEI-OC1 cells and the cochleae of C57BL/6J mice, including auditory brainstem response (ABR) testing, qRT-PCR, Western blotting, Fe detection, and immunofluorescence analysis.

RESULTS

The study identified 20 ferroptosis-related genes associated with hearing loss. Using Lasso and SVM-RFE models, a novel model was constructed, consisting of nine genes ( and ). Among these, were found to be associated with ARHL.

CONCLUSION

Ferroptosis is a potential pathological mechanism in hearing loss research, and the nine ferroptosis-related genes identified provide promising targets for exploring new diagnostics and treatments for hearing loss. Notably, and are associated with ARHL.