Uncovering Novel Prognostic Factors of Sudden Sensorineural Hearing Loss by Whole-Genome Sequencing of Cell-Free DNA.

ABSTRACT

BACKGROUND: Sudden sensorineural hearing loss is a common disease with several etiologic hypotheses, such as infection, vascular occlusion, inflammation, oxidative stress, etc. Studies have reported that the concentration of cell-free DNA in plasma will elevate in these situations. Former studies have reported that the whole-genome sequencing of cell-free DNA has high accuracy and sensitivity in inferring gene expressions. In this study, we plan to use the whole-genome sequencing of cell-free DNA to uncover novel prognostic factors of sudden sensorineural hearing loss and provide new insight into the clinical application of cell-free DNA. METHODS: In this study, 84 sudden sensorineural hearing loss patients (47 in recovery group and 37 in no-recovery group) were enrolled. After whole-genome sequencing of the cell-free DNA, the protein-protein interaction network was constructed using the differentially expressed genes. Multinomial logistics regression analysis was used to analyze the prognostic factors of hearing improvement. RESULTS: In this study, we found distinct patterns of expressed and unexpressed genes in cell-free DNA sequence read depth coverage in sudden sensorineural hearing loss patients. The top centrality hub genes IGF1, NOTCH1, APOE, FAM3C, RPS6KB1, and RELB were identified from the protein-protein interaction network. Multinomial logistics regression analysis demonstrated that the coverage patterns of 3 key differentially expressed genes (NOTCH1, APOE, and RELB) are significantly different in sudden sensorineural hearing loss with and without hearing recovery. CONCLUSION: The cell-free DNA could have more applications in diverse diseases, and the coverage patterns of 3 differentially expressed genes (NOTCH1, APOE, and RELB) are independent prognostic factors of sudden sensorineural hearing loss. Their expression levels may play a critical role in the hearing improvement of sudden sensorineural hearing loss patients.