胞外囊泡DNA中5-羟甲基胞嘧啶分子标志物对突发性聋的疗效预判研究  

5-Hydroxymethylcytosine Signatures in Extracellular Vesicles DNA as Predictive Biomarkers for Sudden Sensorineural Hearing Loss

作　　者：李新建 时晰[4,5] 郭维维 林坚 陈航宇 陈伟 杨仕明 LI Xinjian;SHI Xi;GUO Weiwei;LIN Jian;CHEN Hangyu;CHEN Wei;YANG Shiming(the First Medical Center of PLA General Hospital,Beijing 100853)

机构地区：[1]中国人民解放军总医院第一医学中心,中国人民解放军总医院耳鼻咽喉头颈外科医学部国家耳鼻咽喉疾病临床医学研究中心聋病教育部重点实验室,北京100853 [2]中国人民解放军医学院 [3]中国人民解放军总医院海南医院耳鼻咽喉头颈外科海南省耳鼻咽喉头颈外科疾病临床医学研究中心 [4]海南大学药学院热带生物资源教育部重点实验室,药学院院士工作站 [5]徐州医科大学 [6]北京大学第三医院药剂科

出　　处：《中华耳科学杂志》2024年第2期221-226,共6页Chinese Journal of Otology

基　　金：国家自然科学基金重点国际(地区)联合研究项目(81820108009);国家自然科学基金(81970890);国家重点研发计划项目(2022YFC2402701);海南省自然科学基金(824MS052)。

摘　　要：目的 突发性聋(sudden sensorineural hearing loss, SSNHL)是一种急性感音神经性聋,部分患者治疗效果较差,目前无有效疗效预测指标。5-羟甲基胞嘧啶(5hmC)是一种稳定的表观遗传标志,因其在不同身体状态下富集含量不同的特点可作为预测疗效的生物标志物,本研究通过寻找5hmC标志物,探索其对SSNHL疗效进行预测的可能性。方法 选取2021年7月—2023年6月中国人民解放军总医院海南医院耳鼻咽喉头颈外科收治的SSNHL患者57例,其中男性26例、女性31例;根据治疗前后的听力结果将患者分为有效组27例和无效组30例。使用队列研究方法,寻找5hmC富集水平与SSNHL疗效之间的相关性。利用5hmC-Seal技术在患者治疗前的血浆胞外囊泡DNA中生成全基因组5hmC谱,比较两组不同治疗效果的5hmC谱,筛选出有价值的5hmC标志物,并进行相关功能和传导通路的初步探索。结果 共鉴定出11个5hmC标志物来预测治疗结果(曲线下面积为0.998),预测准确性较高。GO功能分析表明,调节GTPase活性、神经元投射发育、神经细胞发育等信号通路可能与内耳疾病的发病机制有关。结论 SSNHL治疗有效组和无效组的5hmC谱存在明显差异,胞外囊泡DNA来源的5hmC有可能作为有效的表观遗传生物标志物,用于SSNHL的微创疗效预测。Objective Sudden sensorineural hearing loss(SSNHL)is an acute sensorineural hearing loss,with poor treatment outcomes in some patients.Currently,there are no indicators to effectively predict treatment outcomes.5-hydroxymethylcytosine(5hmC)is a relatively stable epigenetic marker,which can be used as a biomarker for predicting therapeutic effects for its different enrichment levels in different physical states.This study aims to investigate the possibility of predicting the therapeutic effect using 5hmC markers in SSNHL.Methods SSNHL patients admitted to the Department of Otolaryngology,Head and Neck Surgery at Hainan Hospital of the PL A General Hospital from July 2021 to June 2023(n=57,26 males and 31 females)were categorized as treatment responders(n=27)and non-responders(n=30).The correlation between 5hmC enrichment levels and treatment outcomes was evaluated.Using the hmC-Seal technique,the whole genome 5hmC spectrum was generated from the plasma EVsDNA.Potentially indicative 5hmC molecular markers were identified by comparison between the responders and non-responders,and their functions and transmission pathways were assessed using the GO analysis.Results A total of 115hmC markers were identified as potentially predictive of treatment outcomes(AUC=0.998).GO functional analysis indicated that regulating signaling pathways were related to the pathogenesis of inner ear diseases.Conclusions Our findings suggest that the EVsDNA 5hmC can serve as an effective epigenetic biomarker as a minimally noninvasive treatment outcome predictor in SSNHL.

关 键 词：突发性聋 DNA去甲基化 5-羟甲基胞嘧啶 治疗预测 

分 类 号：R764.437[医药卫生—耳鼻咽喉科]