Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
Department of Neurosurgery, Peking University Shenzhen Hospital, Shenzhen, China.
Hear Res. 2023 Nov;439:108894. doi: 10.1016/j.heares.2023.108894. Epub 2023 Oct 5.
Age-related hearing loss (ARHL) or presbycusis is the phenomenon of hearing loss due to the aging of auditory organs with age. It seriously affects the cognitive function and quality of life of the elderly. This study is based on comprehensive bioinformatic and machine learning methods to identify the critical genes of ARHL and explore its therapy targets and pathological mechanisms. The ARHL and normal samples were from GSE49543 datasets of the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was applied to obtain significant modules. The Limma R-package was used to identify differentially expressed genes (DEGs). The 15 common genes of the practical module and DEGs were screened. Functional enrichment analysis suggested that these genes were mainly associated with inflammation, immune response, and infection. Cytoscape software created the protein-protein interaction (PPI) layouts and cytoHubba, support vector machine-recursive feature elimination (SVM-RFE), and random forests (RF) algorithms screened hub genes. After validating the hub gene expressions in GSE6045 and GSE154833 datasets, Clec4n, Mpeg1, and Fcgr3 are highly expressed in ARHL and have higher diagnostic efficacy for ARHL, so they were identified as hub genes. In conclusion, Clec4n, Mpeg1, and Fcgr3 play essential roles in developing ARHL, and they might become vital targets in ARHL diagnosis and anti-inflammatory therapy.
年龄相关性听力损失（ARHL）或老年性聋是指听觉器官随年龄增长而出现的听力损失现象。它严重影响老年人的认知功能和生活质量。本研究基于综合生物信息学和机器学习方法，鉴定 ARHL 的关键基因，并探讨其治疗靶点和病理机制。ARHL 和正常样本均来自基因表达综合数据库（GEO）中的 GSE49543 数据集。应用加权基因共表达网络分析（WGCNA）获得显著模块。使用 Limma R 包鉴定差异表达基因（DEGs）。筛选出实用模块和 DEGs 的 15 个共同基因。功能富集分析表明，这些基因主要与炎症、免疫反应和感染有关。Cytoscape 软件构建蛋白-蛋白相互作用（PPI）布局和 cytoHubba、支持向量机递归特征消除（SVM-RFE）和随机森林（RF）算法筛选枢纽基因。在 GSE6045 和 GSE154833 数据集验证了枢纽基因的表达后，Clec4n、Mpeg1 和 Fcgr3 在 ARHL 中表达较高，对 ARHL 具有较高的诊断效能，因此被鉴定为枢纽基因。综上所述，Clec4n、Mpeg1 和 Fcgr3 在 ARHL 的发生发展中起重要作用，它们可能成为 ARHL 诊断和抗炎治疗的重要靶点。
