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Background <p>Sudden sensorineural hearing loss (SSNHL) is an abrupt, often idiopathic hearing decline with uncertain prognosis and multifactorial pathophysiology. Among its subtypes, total deafness—also referred to as profound SSNHL—carries the worst and most unpredictable prognosis, highlighting an urgent need for reliable biomarkers, especially for prognostic biomarkers. Recent studies have emphasized the potential of exosome microRNAs (miRNAs) as both biomarkers and therapeutic targets in SSNHL, yet very few studies have focused on the profound type. This study aims to preliminarily identify the plasma-derived exosome miRNAs as candidate biomarkers, particularly possible prognostic indicators, in patients with profound SSNHL.</p> Methods <p>Of 32 patients with profound SSNHL, six who achieved complete recovery and six age-matched patients with no improvement after two weeks of glucocorticoid therapy were selected for this retrospective study. Six age-matched healthy individuals with normal hearing served as controls. Pretreatment plasma samples were collected, exosomes purified and stored at -80℃. The exosome samples from 18 enrolled participants were subjected to RNA extraction and small RNA sequencing. Differentially expressed exosome miRNAs (DEEMs) were identified using the DESeq R package, with significance thresholds set at <i>p</i> &lt; 0.05 and |log₂(fold change)| &gt; 1. Predicted target mRNAs of DEEMs between the recovery and no improvement groups were analyzed for pathway enrichment using the Metascape database.</p> Results <p>We identified 12 candidate DEEMs (10 downregulated and 2 upregulated) shared across all profound SSNHL groups compared to healthy controls, and 14 candidate DEEMs (6 downregulated and 8 upregulated) between the no improvement group and the recovery group. The six pronounced changed miRNAs out of those 14 were hsa-miR-320d, hsa-miR-146a-3p, hsa-miR-132-3p, hsa-miR-9-3p, hsa-miR-219b-5p, and hsa-miR-219a-2-3p. The target mRNAs of these top six miRNAs were mainly enriched in pathways of embryonic development, tube morphogenesis, cell division, synaptic transmission, STAT3 and TGF-β signaling, autophagy, cellular import, ketone response, and cellular responses to interleukin-1 and stress.</p> Conclusions <p>By exosomal miRNA profiling from patients of different treatment outcomes,, this exploratory study initially identified potential DEEMs that may serve as candidate biomarkers for profound SSNHL, although larger, independently replicated studies are required.</p>

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Differentially expressed exosome miRNA profiles as putative prognostic biomarkers for profound sudden sensorineural hearing loss

  • 期刊论文

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  • 发表日期：

    2026年2月24日

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  • Hongru Zhang,
  • Haoliang Xie,
  • Qiran Cao,
  • Ping Chen,
  • Sen Yan,
  • Xin Zhang,
  • Pei Gao,
  • Yu Zhang

摘要

Background

Sudden sensorineural hearing loss (SSNHL) is an abrupt, often idiopathic hearing decline with uncertain prognosis and multifactorial pathophysiology. Among its subtypes, total deafness—also referred to as profound SSNHL—carries the worst and most unpredictable prognosis, highlighting an urgent need for reliable biomarkers, especially for prognostic biomarkers. Recent studies have emphasized the potential of exosome microRNAs (miRNAs) as both biomarkers and therapeutic targets in SSNHL, yet very few studies have focused on the profound type. This study aims to preliminarily identify the plasma-derived exosome miRNAs as candidate biomarkers, particularly possible prognostic indicators, in patients with profound SSNHL.

Methods

Of 32 patients with profound SSNHL, six who achieved complete recovery and six age-matched patients with no improvement after two weeks of glucocorticoid therapy were selected for this retrospective study. Six age-matched healthy individuals with normal hearing served as controls. Pretreatment plasma samples were collected, exosomes purified and stored at -80℃. The exosome samples from 18 enrolled participants were subjected to RNA extraction and small RNA sequencing. Differentially expressed exosome miRNAs (DEEMs) were identified using the DESeq R package, with significance thresholds set at p < 0.05 and |log₂(fold change)| > 1. Predicted target mRNAs of DEEMs between the recovery and no improvement groups were analyzed for pathway enrichment using the Metascape database.

Results

We identified 12 candidate DEEMs (10 downregulated and 2 upregulated) shared across all profound SSNHL groups compared to healthy controls, and 14 candidate DEEMs (6 downregulated and 8 upregulated) between the no improvement group and the recovery group. The six pronounced changed miRNAs out of those 14 were hsa-miR-320d, hsa-miR-146a-3p, hsa-miR-132-3p, hsa-miR-9-3p, hsa-miR-219b-5p, and hsa-miR-219a-2-3p. The target mRNAs of these top six miRNAs were mainly enriched in pathways of embryonic development, tube morphogenesis, cell division, synaptic transmission, STAT3 and TGF-β signaling, autophagy, cellular import, ketone response, and cellular responses to interleukin-1 and stress.

Conclusions

By exosomal miRNA profiling from patients of different treatment outcomes,, this exploratory study initially identified potential DEEMs that may serve as candidate biomarkers for profound SSNHL, although larger, independently replicated studies are required.