Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy.
Circulating MicroRNAs From Plasma Small Extracellular Vesicles as Potential Diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy.
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来自血浆小细胞外囊泡的循环微RNA作为儿科癫痫和耐药性癫痫的潜在诊断生物标志物。
DOI：
10.3389/fnmol.2022.823802
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发表时间：
2022
影响因子：
4.8
通讯作者：
Gao F
中科院分区：
文献类型：
--
作者：
Wang Y;Wang Y;Chen Y;Hua Y;Xu L;Zhu M;Zhao C;Zhang W;Sheng G;Liu L;Jiang P;Yuan Z;Zhao Z;Gao F
小儿癫痫是一种神经系统疾病，导致反复和无端癫痫发作，在1-5岁儿童中更常见。耐药性已被认为是改善儿童癫痫患者临床结局的关键挑战。在本研究中，我们的目的是确定血浆小细胞外囊泡（sEVs）衍生的microRNA（miRNAs）从儿童血浆样本中预测癫痫和耐药癫痫患者的预后。共有90名临床诊断为癫痫的儿童[46名抗癫痫药物（AED）反应性癫痫和44名耐药性癫痫]和37名健康对照（HC）入组本研究。进行RNA测序以鉴定从儿童血浆样品中分离的血浆sEV衍生的miRNA。使用生物信息学工具鉴定差异表达的血浆sEV衍生的miRNA，并通过逆转录-聚合酶链反应和受试者工作特征（ROC）曲线分析进一步验证。在本研究中，选择了6种miRNA（hsa-miR-125 b-5 p、hsa-miR-150- 3 p、hsa-miR-199 a-3 p、hsa-miR-584- 5 p、hsa-miR-199 a-5 p和hsa-miR-342- 5 p）用于进一步验证。曲线下面积（AUC）值分别为0.846、0.835和0.826的hsa-miR-584- 5 p、hsa-miR-342- 5 p和hsa-miR-150- 5 p被鉴定为癫痫的有希望的生物标志物。组合三种miRNA（hsa-miR-584- 5 p、hsa-miR-342- 5 p和hsa-miR-199 a-3 p）的逻辑模型可以达到0.883的AUC，并且六种miRNA模型（hsa-miR-342- 5 p、hsa-miR-584- 5 p、hsa-miR-150- 5 p、hsa-miR-125 b-5 p、hsa-miR-199 a-3 p和hsa-miR-199 a-5 p）可以达到0.888的AUC。评估了多个miRNA组的预测概率，以区分耐药儿童和药物反应儿童。六种miRNA组（hsa-miR-342- 5 p、hsa-miR-584- 5 p、hsa-miR-150- 5 p、hsa-miR-125 b-5 p、hsa-miR-199 a-3 p和hsa-miR-199 a-5 p）的AUC达到0.823。我们鉴定并确认了血浆sEV来源的miRNA生物标志物，这些生物标志物可被视为儿科癫痫和耐药癫痫的潜在治疗靶点。
Pediatric epilepsy is a neurological condition that causes repeated and unprovoked seizures and is more common in 1–5-year-old children. Drug resistance has been indicated as a key challenge in improving the clinical outcomes of patients with pediatric epilepsy. In the present study, we aimed to identify plasma small extracellular vesicles (sEVs) derived microRNAs (miRNAs) from the plasma samples of children for predicting the prognosis in patients with epilepsy and drug-resistant epilepsy. A total of 90 children clinically diagnosed with epilepsy [46 antiepileptic drug (AED)-responsive epilepsy and 44 drug-resistant epilepsy] and 37 healthy controls (HCs) were enrolled in this study. RNA sequencing was performed to identify plasma sEVs derived miRNAs isolated from the children’s plasma samples. Differentially expressed plasma sEVs derived miRNAs were identified using bioinformatics tools and were further validated by reverse transcription-polymerase chain reaction and receiver operator characteristic (ROC) curve analysis. In the present study, 6 miRNAs (hsa-miR-125b-5p, hsa-miR-150-3p, hsa-miR-199a-3p, hsa-miR-584-5p hsa-miR-199a-5p, and hsa-miR-342-5p) were selected for further validation. hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-150-5p with area under curve (AUC) values of 0.846, 0.835, and 0.826, respectively, were identified as promising biomarkers of epilepsy. A logistic model combining three miRNAs (hsa-miR-584-5p, hsa-miR-342-5p, and hsa-miR-199a-3p) could achieve an AUC of 0.883 and a six miRNAs model (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) could attain an AUC of 0.888. The predicted probability of multiple miRNA panels was evaluated for differentiating between drug-resistant children and drug-responsive children. The AUC of a six-miRNA panel (hsa-miR-342-5p, hsa-miR-584-5p, hsa-miR-150-5p, hsa-miR-125b-5p, hsa-miR-199a-3p, and hsa-miR-199a-5p) reached 0.823. We identified and confirmed plasma sEVs derived miRNA biomarkers that could be considered as potential therapeutic targets for pediatric epilepsy and drug-resistant epilepsy.
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DOI：
10.1007/s00018-018-2773-4
发表时间：
2018-08
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Karimi N;Cvjetkovic A;Jang SC;Crescitelli R;Hosseinpour Feizi MA;Nieuwland R;Lötvall J;Lässer C
通讯作者：
Lässer C
影响因子：
4.3
作者：
Cukovic D;Bagla S;Ukasik D;Stemmer PM;Jena BP;Naik AR;Sood S;Asano E;Luat A;Chugani DC;Dombkowski AA
通讯作者：
Dombkowski AA
影响因子：
5.6
作者：
De Benedittis S;Fortunato F;Cava C;Gallivanone F;Iaccino E;Caligiuri ME;Castiglioni I;Bertoli G;Manna I;Labate A;Gambardella A
通讯作者：
Gambardella A
影响因子：
3.1
作者：
Hajjri, Seyedeh Nazanin;Sadigh-Eteghad, Saeed;Mehdizadeh, Mehdi
通讯作者：
Mehdizadeh, Mehdi
影响因子：
25.7
作者：
Komoll, Ronja-Melinda;Hu, Qingluan;Balakrishnan, Asha
通讯作者：
Balakrishnan, Asha