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铁死亡相关生物标志物在听力损失诊断和治疗靶点中的实验验证与鉴定

Experimental validation and identification of ferroptosis-associated biomarkers for diagnostic and therapeutic targeting in hearing loss.

作者信息

Yuan Chenyang, Ma Tianyu, Liu Mengting, Jiang Li, Tang Gongrui, Hu Qi, Zhang Tianhong

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Front Aging Neurosci. 2025 Apr 25;17:1526519. doi: 10.3389/fnagi.2025.1526519. eCollection 2025.

DOI:10.3389/fnagi.2025.1526519
PMID:40353062
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12062182/
Abstract

OBJECTIVES

Ferroptosis, a regulated form of cell death, has attracted significant attention in hearing loss research; however, the role of ferroptosis-related genes remains unclear. This study aimed to clarify diagnostic and therapeutic targeting of ferroptosis-related genes in hearing loss.

METHODS

Differentially expressed genes related to hearing loss from the GEO database were intersected with ferroptosis-related genes. The Lasso and SVM-RFE models were applied to reduce the gene set, identifying model genes. Biological functions, pathways, and gene-drug associations related to these model genes were analyzed. Age-related hearing loss (ARHL) genes within the model genes were obtained from a genome-wide association study (GWAS) dataset. Further validation was conducted in HEI-OC1 cells and the cochleae of C57BL/6J mice, including auditory brainstem response (ABR) testing, qRT-PCR, Western blotting, Fe detection, and immunofluorescence analysis.

RESULTS

The study identified 20 ferroptosis-related genes associated with hearing loss. Using Lasso and SVM-RFE models, a novel model was constructed, consisting of nine genes ( and ). Among these, were found to be associated with ARHL.

CONCLUSION

Ferroptosis is a potential pathological mechanism in hearing loss research, and the nine ferroptosis-related genes identified provide promising targets for exploring new diagnostics and treatments for hearing loss. Notably, and are associated with ARHL.

摘要

目的

铁死亡是一种受调控的细胞死亡形式，在听力损失研究中已引起广泛关注；然而，铁死亡相关基因的作用仍不清楚。本研究旨在阐明听力损失中铁死亡相关基因的诊断和治疗靶点。

方法

将来自基因表达综合数据库（GEO数据库）的与听力损失相关的差异表达基因与铁死亡相关基因进行交叉分析。应用套索回归和支持向量机递归特征消除（SVM-RFE）模型来减少基因集，从而识别模型基因。对与这些模型基因相关的生物学功能、信号通路和基因-药物关联进行分析。从全基因组关联研究（GWAS）数据集中获取模型基因内与年龄相关性听力损失（ARHL）相关的基因。在HEI-OC1细胞和C57BL/6J小鼠的耳蜗中进行进一步验证，包括听觉脑干反应（ABR）测试、实时定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法、铁检测和免疫荧光分析。

结果

该研究确定了20个与听力损失相关的铁死亡相关基因。使用套索回归和SVM-RFE模型构建了一个由9个基因组成的新模型。其中，发现[具体基因名称]与ARHL相关。

结论

铁死亡是听力损失研究中的一种潜在病理机制，所确定的9个铁死亡相关基因可为探索听力损失的新诊断方法和治疗方法提供有前景的靶点。值得注意的是，[具体基因名称]与ARHL相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/31f96585e6a8/fnagi-17-1526519-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/98925977d49c/fnagi-17-1526519-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/26baa0cef4fc/fnagi-17-1526519-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/79553506299b/fnagi-17-1526519-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/2cf9f92c8422/fnagi-17-1526519-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/6c153b39da7b/fnagi-17-1526519-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/760857fa3f6d/fnagi-17-1526519-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/80eca408b119/fnagi-17-1526519-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/cf3291e89cc8/fnagi-17-1526519-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/31f96585e6a8/fnagi-17-1526519-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/98925977d49c/fnagi-17-1526519-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/26baa0cef4fc/fnagi-17-1526519-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/79553506299b/fnagi-17-1526519-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/2cf9f92c8422/fnagi-17-1526519-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/6c153b39da7b/fnagi-17-1526519-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/760857fa3f6d/fnagi-17-1526519-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/80eca408b119/fnagi-17-1526519-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/cf3291e89cc8/fnagi-17-1526519-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f548/12062182/31f96585e6a8/fnagi-17-1526519-g009.jpg

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