Integrative multi-dataset analysis identifies immune-inflammatory hub genes as diagnostic biomarkers and therapeutic targets for age-related hearing loss.

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research Pub Date : 2025-10-09 DOI:10.1016/j.heares.2025.109448

Xiaoqin Luo, Wei Yuan, Jun Liu, Chanyuan Zhang, Chao Li, Gang Qin

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引用次数: 0

Abstract

Age-related hearing loss (ARHL) is a common neurodegenerative disorder in the elderly, but its molecular mechanisms and diagnostic biomarkers remain unclear. Here, by using the GSE49543 dataset (n = 40, Affymetrix microarray) from the Gene Expression Omnibus (GEO) with limma, 17 ARHL-associated differentially expressed genes were identified, which were enriched in immune effector functions and the IL-17 signaling pathway. Weighted gene co-expression network analysis (WGCNA) further revealed that 168 genes were associated with hearing loss (module significance > 0.3). Intersecting DEGs with this module yielded 15 candidates, which were prioritized via protein-protein interaction (PPI) network (STRING) and CytoHubba algorithms to 7 core genes. Machine learning refined these to 5 hub genes: Fcgr3, Cd68, Lgals3, Laptm5, and Mpeg1, showing excellent diagnostic performance. Validation in five independent transcriptomic datasets (GSE49543, GSE6045, GSE153882, GSE154833, and GSE233798) confirmed their upregulation in ARHL samples, and experimental verification via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) further validated elevated mRNA (FCGR3, CD68, LGALS3, MPEG1) and protein (FCGR3, CD68, LGALS3) levels in aged mouse cochleae. Additionally, single-nucleus RNA sequencing (snRNA-seq) dataset GSE274279 was integrated to validate hub gene expression at single-cell resolution. These findings identify Fcgr3, Cd68, Lgals3, Laptm5, and Mpeg1 as immune-inflammatory hub genes with potential as diagnostic biomarkers and therapeutic targets for ARHL.

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综合多数据集分析确定免疫炎症中心基因作为年龄相关性听力损失的诊断生物标志物和治疗靶点。

年龄相关性听力损失（ARHL）是老年人常见的神经退行性疾病，但其分子机制和诊断生物标志物尚不清楚。本研究利用来自Gene Expression Omnibus （GEO）与limma的GSE49543数据集（n = 40， Affymetrix微阵列），鉴定了17个与arhl相关的差异表达基因，这些基因在免疫效应功能和IL-17信号通路中富集。加权基因共表达网络分析（WGCNA）进一步揭示了168个与听力损失相关的基因（模块显著性> 0.3）。与该模块相交的deg产生15个候选基因，通过蛋白蛋白相互作用（PPI）网络（STRING）和CytoHubba算法对7个核心基因进行优先排序。机器学习将这些基因提炼为5个枢纽基因：Fcgr3、Cd68、Lgals3、Laptm5和Mpeg1，表现出出色的诊断性能。在5个独立的转录组数据集（GSE49543、GSE6045、GSE153882、GSE154833和GSE233798）中验证了它们在ARHL样本中的上调，并通过实时荧光定量PCR （qRT-PCR）和免疫组化（IHC）进一步验证了衰老小鼠耳蜗中mRNA （FCGR3、CD68、LGALS3、MPEG1）和蛋白（FCGR3、CD68、LGALS3）水平升高。此外，还整合了单核RNA测序（snRNA-seq）数据集GSE274279，以验证单细胞分辨率下枢纽基因的表达。这些发现确定Fcgr3、Cd68、Lgals3、Laptm5和Mpeg1是免疫炎症中心基因，具有作为ARHL诊断生物标志物和治疗靶点的潜力。

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来源期刊

Hearing Research 医学-耳鼻喉科学

CiteScore

5.30

自引率

14.30%

发文量

163

审稿时长

75 days

期刊介绍： The aim of the journal is to provide a forum for papers concerned with basic peripheral and central auditory mechanisms. Emphasis is on experimental and clinical studies, but theoretical and methodological papers will also be considered. The journal publishes original research papers, review and mini- review articles, rapid communications, method/protocol and perspective articles. Papers submitted should deal with auditory anatomy, physiology, psychophysics, imaging, modeling and behavioural studies in animals and humans, as well as hearing aids and cochlear implants. Papers dealing with the vestibular system are also considered for publication. Papers on comparative aspects of hearing and on effects of drugs and environmental contaminants on hearing function will also be considered. Clinical papers will be accepted when they contribute to the understanding of normal and pathological hearing functions.