Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease.
Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson's disease.
复制标题
DOI：
10.1186/s40035-021-00249-y
复制
发表时间：
2021-07-28
影响因子：
12.6
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
He S;Huang L;Shao C;Nie T;Xia L;Cui B;Lu F;Zhu L;Chen B;Yang Q
基于血液检测预测疾病进展和早期诊断帕金森病（PD）是一个未满足的临床需求。microRNAs （miRNAs）的谱被认为是人类疾病的潜在诊断生物标志物，而外周的miRNAs容易受到各种成分的影响。血清细胞外囊泡（EVs）中富集的mirna由于其高丰度、稳定性和抗降解性，在诊断疾病方面具有特异性优势。本研究旨在筛选健康对照和PD患者之间表达差异的ev衍生mirna，以帮助PD的诊断。研究对象为唐都医院经不同Hoehn和Yahr分期诊断为PD的患者72例和健康对照31例。通过血清EVs的RNA测序以及edgeR和t检验分析，共获得185个差异表达的mirna。随后，利用加权基因共表达网络分析（weighted gene co-expression network analysis， WGCNA），通过构建模块间的连接，鉴定PD各阶段共同表达的mirna，并通过功能富集分析，特异性表达PD各阶段的mirna。将这些miRNA与人类miRNA疾病数据库中的pd相关miRNA进行比对后，使用另外40名参与者的外周血ev，通过受试者工作特征（ROC）曲线和定量实时聚合酶链反应（qRT-PCR）进一步验证筛选的miRNA。WGCNA结果显示，4种mirna与PD的所有分期普遍相关，13种mirna与PD的不同分期特异性相关。在获得的17个mirna中，有7个通过ROC曲线分析验证，另外40个参与者中有7个通过qRT-PCR验证。两种方法共验证了6种mirna，其中2种mirna普遍表达于PD的所有阶段，4种mirna特异性表达于PD的不同阶段。6种血清ev衍生的mirna， hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p， hsa-miR-22-5p和hsa-miR-151a-5p，可能潜在地用作PD进展的生物标志物和人群中PD的早期诊断。在线版本包含补充资料，可在10.1186/s40035-021-00249-y获得。
Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations. The online version contains supplementary material available at 10.1186/s40035-021-00249-y.
登录
查看更多内容
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
8.6
作者：
Cressatti, Marisa;Juwara, Lamin;Schipper, Hyman M.
通讯作者：
Schipper, Hyman M.
影响因子：
81.5
作者：
Poewe, Werner;Seppi, Klaus;Lang, Anthony E.
通讯作者：
Lang, Anthony E.
影响因子：
5.6
作者：
Leggio L;Vivarelli S;L'Episcopo F;Tirolo C;Caniglia S;Testa N;Marchetti B;Iraci N
通讯作者：
Iraci N