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使用下一代测序技术鉴定血浆微小RNA-206作为导管消融术后心房颤动早期复发的新预测指标

Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.

作者信息

Šustr Filip, Macháčková Táňa, Pešl Martin, Svačinova Jana, Trachtová Karolína, Stárek Zdeněk, Kianička Bohuslav, Slabý Ondřej, Novák Jan

机构信息

2nd Department of Internal Medicine, St. Anne's University Hospital in Brno and Faculty of Medicine of Masaryk University, Pekařská 53, 602 00, Brno, Czech Republic.

Department of Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

出版信息

Mol Diagn Ther. 2024 May;28(3):301-310. doi: 10.1007/s40291-024-00698-x. Epub 2024 Mar 8.

Abstract

BACKGROUND

Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs).

METHODS

A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants.

RESULTS

Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression.

CONCLUSION

We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.

摘要

背景

导管消融(CA)治疗心房颤动(AF)适用于有复发性和症状性AF发作的患者。尽管有严格的纳入/排除标准,但CA术后AF复发率仍然很高。识别一种能够预测AF复发的新型生物标志物将有助于对患者进行分层。本研究的目的是在血浆微小RNA(miRNA,miRs)中寻找新型生物标志物。

方法

进行了一项前瞻性单中心研究。共纳入49例连续的适合CA治疗的AF患者。在CA术前进行血液采样。使用商业试剂盒从血浆中分离RNA。在探索阶段,使用Illumina仪器对10例AF患者(5例有AF复发,5例无AF复发)进行小RNA测序。在验证阶段,使用定量逆转录聚合酶链反应(qRT-PCR)测定所有参与者中选定miRNA的水平。

结果

通过下一代测序(使用DESeq2算法)共鉴定出22种miRNA在两组之间存在差异。使用qRT-PCR在整个队列中验证了5种变化最大的miRNA(miR-190b/206/326/505-5p/1296-5p)的水平。早期(6个月内)AF复发患者的hsa-miR-206血浆水平显著更高,并且在二元逻辑回归中显示其水平每增加1个单位,复发风险增加2.65倍。

结论

我们已经鉴定出一组22种血浆miRNA,它们在CA术后有AF复发和无AF复发的患者之间存在差异,并证实hsa-miR-206是一种与早期AF复发相关的新型miRNA。结果应在更大的独立队列中进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f87d/11068688/e63d44ab5c61/40291_2024_698_Figa_HTML.jpg

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