目的 分析脐带血miR-431表达水平与新生儿先天性听力障碍的关系,为先天性听力障碍的临床防治提供参考依据。方法 选取2017年5月—2019年6月成都市郫都区人民医院耳鼻喉科收治的80例先天性听力障碍新生儿作为病例组,另外同期选取30例听力正常新生儿作为正常组。比较两组新生儿听性脑干反应(ABR)测试阈值和脐带血miR-431、miR-183、miR-96表达水平,采用ROC曲线分析脐带血miR-431、miR-183水平对轻中、重度听力障碍的鉴别价值。结果 短声产生后病例组左、右耳ABR测试阈值均明显高于正常组(t=22.166、19.741,P＜0.05);病例组患儿的miR-431水平明显高于正常组,miR-183水平明显低于正常组(t=15.445、19.607,P＜0.05);重度组患儿miR-431水平明显高于轻中度组,miR-183水平明显低于轻中度组(t=10.047、11.816,P＜0.05);miR-431鉴别轻中、重度听力障碍的曲线下面积(AUC)为0.835(95%CI:0.735~0.908,P＜0.001),界值为0.48,敏感度与特异度为77.78%、86.36%;miR-183鉴别轻中、重度听力障碍的AUC为0.804(95%CI:0.700~0.884,P＜0.001),界值为0.25,敏感度与特异度为72.22%、84.09%。结论 先天性听力障碍新生儿的左、右耳ABR阈值明显高于正常儿童,同时患儿脐带血miR-431表达异常上调,miR-183表达水平下调,且miR-431、miR-183具有较好地鉴别轻中、重度听力障碍的效能。
Abstract
Objective To study the relationship between cord blood miR-431 and congenital hearing disorders in neonates, so as to provide reference for clinical prevention and treatment of congenital hearing impairment. Methods From May 2017 to June 2019, 80 neonates with congenital hearing disorder admitted to the Department of Obstetrics and Gynecology, Pidu District People′s Hospital were enrolled as case group, while another 30 neonates with normal hearing were selected into normal group. The threshold of auditory brainstem response(ABR) test, and expression levelsof cord blood miR-431, miR-183 and miR-96 were compared between the two groups. The identification value of miR-431 and miR-183 for mild, moderate and severe hearing disorder was analyzed by ROC curve. Results After click, thresholds of left and right ears in ABR test in case group were significantly higher than those in normal group(t=22.166, 19.741, P<0.05). The miR-431 level in case group was significantly higher than that in normal group, while miR-183 level was significantly lower than that in normal group(t=15.445, 19.607, P<0.05). The miR-431 level in severe hearing disorder group was significantly higher than that in mild-to-moderate hearing disorder group, while miR-183 level was significantly lower than that in mild-to-moderate hearing disorder group(t=10.047,11.816,P<0.05). When the cut-off value of miR-431 was 0.48, the area under the curve(AUC) in discriminating mild, moderate and severe hearing disorder was 0.835(95%CI: 0.735 - 0.908, P<0.001).The sensitivity and specificity were 77.78% and 86.36%, respectively. When the cut-off value of miR-183 was 0.25, the area under the curve(AUC) in discriminating mild, moderate and severe hearing loss was 0.804(95%CI: 0.700 - 0.884, P<0.001).The sensitivity and specificity were 72.22% and 84.09%, respectively. Conclusions The left and right ear ABR thresholds of newborns with congenital hearing disorder are significantly higher than those of normal neonates, while the expression level of miR-431 in cord blood is abnormally up-regulated, while expression level of miR-183 is down-regulated. The miR-431 and miR-183 have better efficacy in discriminating mild, moderate and severe hearing disorder.
关键词
脐带血 /
miR-431 /
先天性听力障碍 /
新生儿
Key words
cord blood /
miR-431 /
congenital hearing disorder /
neonate
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参考文献
[1] 姚聪,胡艳玲,周爱芬,等. 武汉市新生儿听力与耳聋基因联合筛查模式的建立[J].中国优生与遗传杂志,2017,25(8):93-95.
Yao C, Hu YL, Zhou AF, et al.Establishment of a joint screening model for newborn hearing and deafness genes in Wuhan[J]. Chin J Eug Gene, 2017, 25 (8):93-95.
[2] 冯永,马璐. 遗传性耳聋致病基因的研究现状[J].医学临床研究,2020, 37(4):481-485.
Feng Y, Ma L.Research status of pathogenic genes of hereditary deafness[J].Med Clin Res, 2020, 37 (4):481-485
[3] 陈丁莉,李守霞,郭丽丽,等. 冀南地区646例新生儿脐带血常见耳聋基因突变的高通量筛查[J].中国妇幼保健,2016,31(19):4004-4008.
Chen DL, Li SX, Guo LL, et al.High throughput screening of common deafness gene mutations in 646 newborn umbilical cord blood in southern Hebei[J]. Mat Chi Health Care Clin,2016, 31 (19):4004-4008.
[4] 王雪瑶,黄丽辉,杜亚婷. 儿童迟发性听力损失病因学研究进展[J].中华耳鼻咽喉头颈外科杂志,2017,52(10):787-791.
Wang XY, Huang LH, Du YT.Research progress in etiology of delayed hearing loss in children[J]. Chin J Oto Head Neck Sur, 2017, 52 (10):787-791.
[5] LeeKP,Shin YJ,Panda AC, et al. miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4[J].Genes Dev,2015, 29(15):1605-1617.
[6] Elkan-Miller T,Ulitsky I,Hertzano R,et al.Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear[J]. PLoS One, 2011, 6(4):e18195.
[7] 许政敏. 新生儿听力筛查-诊断-干预[J]. 中华耳鼻咽喉科杂志, 2004, 39(11):698-701.
Xu ZM.Neonatal hearing screening diagnosis intervention[J]. Chin J Oto, 2004, 39 (11):698-701.
[8] 余红, 樊洁敏, 陈晓霞.听力损失婴儿的听力监测[J].中国儿童保健杂志,2010, 18(5):63-65.
Yu H, Fan JM, Chen XX. Hearing monitoring of hearing loss infants[J]. Chin J Chil Health Care, 2010, 18 (5):63-65.
[9] 陈智斌,浦懋懋,姚俊,等. 靶向Notch信号通路与内耳发育相关microRNA的筛选及microRNA-384-5p的实验分析[J].中华耳鼻咽喉头颈外科杂志,2018, 53(11):830-837.
Chen ZB, Pu MM, Yao J, et al.Screening of microRNAs targeting Notch signaling pathway and inner ear development and experimental analysis of microRNA-384-5p[J]. Chin J Otorhinolaryngol Head Neck Surg, 2018, 53 (11):830-837.
[10] 宋超,张宗彪,付四清.miRNA突变与非综合征型感觉神经性耳聋[J].中国妇幼保健,2012,27(27):4302-4304.
Song C, Zhang ZB, Fu SQ.MiRNA mutation and non syndromic sensorineural hearing loss[J]. Mat Chi Health Care Chin, 2012, 27 (27):4302-4304.
[11] Li YM, Li A, Wu JF, et al. MiR-182-5p protects inner ear hair cells from cisplatin-induced apoptosis by inhibiting FOXO3a[J].Cell Death Dis, 2016, 7(9):2362.
[12] Su WB, Liu ZY. MiR-431 inhibits colorectal cancer cell invasion via repressing CUL4B[J].Eur Review Med Pharmacol Sci, 2018, 22(10):3047-3052.
[13] Wertz MH,Winden K, Neveu P, et al. Cell-type-specific miR-431 dysregulation in a motor neuron model of spinal muscular atrophy[J]. Hum Mol Genet, 2016, 25(11):2168-2181.
[14] Liu Y, Li L, Liu Z, et al.Downregulation of MiR-431 expression associated with lymph node metastasis and promotes cell invasion in papillary thyroid carcinoma[J]. Cancer Biomark, 2018, 22(4):727-732.
[15] Wu R, Li H,Zhai L, et al. microRNA-431 accelerates muscle regeneration and ameliorates muscular dystrophy by targeting Pax7 in mice[J]. Nat Commun, 2015(6):7713.
[16] Lewis MA,Domenico FD, Ingham NJ, et al. Hearing impairment due to Mir183/96/182 mutations suggests both loss and gain of function effects[J]. Dis Model Mech, 2020, 14(2):dmm047225.
[17] Fan Y, Zhang Y, Wu RM, et al. miR-431 is involved in regulating cochlear function by targeting Eya4[J].Biochim Biophys Acta, 2016, 1862(11):2119-2126.
[18] 章伟敏, 王耀文, 程鹏, 等. 不同月龄老年性聋小鼠miR-183表达与ROS变化[J]. 中国卫生检验杂志, 2019, 29(13):1557-1560.
Zhang WM, Wang YW, Cheng P, et al.Expression of miR-183 and changes of ROS in aged deaf mice of different months[J].Chin J Health Ins, 2019, 29 (13):1557-1560.
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