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Among its subtypes, total deafness\u2014also referred to as profound SSNHL\u2014carries 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\u2103. 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\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05 and |log\u2082(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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats: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-\u03b2 signaling, autophagy, cellular import, ketone response, and cellular responses to interleukin-1 and stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-026-02330-9","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:04:38Z","timestamp":1771920278000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Differentially expressed exosome miRNA profiles as putative prognostic biomarkers for profound sudden sensorineural hearing loss"],"prefix":"10.1186","volume":"19","author":[{"given":"Hongru","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoliang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiran","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"2330_CR1","doi-asserted-by":"publisher","unstructured":"Nakashima T, Itoh A, Misawa H, Ohno Y. 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The study was performed in accordance with the relevant guidelines and regulations. All procedures involving human participants were in accordance with the ethical standards of the Beijing Haidian Hospital. And the trial was conducted in compliance with the Helsinki Declaration.Written informed consent was obtained from all participants or their legal guardians for study participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"56"}}