Diagnostic Value of Circulating microRNAs for In-Stent Restenosis in Patients with Lower Extremity Arterial Occlusive Disease

Liangxi Yuan,Junmin Bao,Jian Zhou,Jian Dong,Guanglang Zhu,Qingsheng Lu,Zaiping Jing

doi:10.1038/s41598-018-36295-2

Liangxi Yuan, Junmin Bao + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-36295-2

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Abstract

In-stent restenosis (ISR) is still a major cause of failure of endovascular stenting treatment in patients with lower extremity arterial occlusive disease (LEAOD). Sensitive and reliable biomarkers for early diagnosis to predict ISR should be considered. This study was conducted to explore the diagnostic value of microRNA in predicting ISR in patients with LEAOD after endovascular stenting treatment. From March 2014 to July 2016, 208 patients (170 males and 38 females) with LEAOD undergoing interventional treatment were enrolled in this research. Patients were divided into the restenosis and non-restenosis groups according to routine postoperative angiography. Circulating microRNAs expression were detected in 208 participants, including 78 ISR patients, 68 non-ISR patients and 62 healthy volunteers. We selected 6 microRNAs from microarray screening as candidates for further testing via qRT-PCR. A receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of circulating microRNAs in predicting ISR for LEAOD patients. The results showed that circulating microRNA-320a and microRNA-572 in patients with ISR (n = 78) had significantly higher expression levels than it from non-ISR and healthy volunteers. By receiver operating characteristic curve analysis, the sensitivity was 82.1% and the specificity was 63.8% for microRNA-320a; the sensitivity was 69.2% and the specificity was 68.9% for microRNA-572, and the AUC was 0.766 and 0.690 for detection of ISR, respectively. Furthermore, 78 patients with ISR had significantly higher circulating expression levels of microRNA-3937 and microRNA-642a-3p and lower circulating expression levels of microRNA-4669 and microRNA-3138 compared with 68 non-ISR patients and 62 healthy volunteers, but they have no significant difference. We found that differential circulating microRNA expression in patients after stenting with ISR, and the data indicate that circulating microRNA-320a and microRNA-572 have promising value in diagnosing ISR in patients with LEAOD.

Highlights

MicroRNAs are a kind of small, single-stranded noncoding RNAs, which control various biological functions and play important roles in physiologic and pathologic processes by inducing mRNA degradation and translation interruption[3]
All assays of samples from 8 In-stent restenosis (ISR) patients, 5 non-ISR patients and 4 healthy volunteers were successfully conducted on plasma specimens used to screen the significant differential expression levels of microRNAs with the microarray containing probes
The 6 differentially expressed microRNAs were identified as candidates and were tested using the entire sample set (78 ISR patients, 68 non-ISR patients and 62 healthy volunteers) with quantitative real-time polymerase chain reaction (qRT-PCR), and all the 6 microRNAs passed quality control

Summary

Introduction

MicroRNAs (microRNAs) are a kind of small (approximately 22 nucleotides), single-stranded noncoding RNAs, which control various biological functions and play important roles in physiologic and pathologic processes by inducing mRNA degradation and translation interruption[3]. Increasing evidence indicates that microRNAs regulate diverse cellular functions, such as proliferation[4] and apoptosis[5]. These microRNAs must have been association with the development of cardiovascular diseases. Yu et al detected serum microRNA-143 expression by using quantitative real-time polymerase chain reaction (qRT-PCR) and found that microRNA-143 can be a promising tool for predicting the ISR in patients with lower extremity arterial occlusive disease[10]. The purpose of this study was to investigate the expression of circulating microRNA from microarray screening and qRT-PCR and assessed its diagnostic value in patients after stenting with and without ISR, and to provide evidence for early detection of restenosis after stenting

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