Exosome-Derived MiRNAs as Biomarkers of the Development and Progression of Intracranial Aneurysms

Abstract

Aim: Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of intracranial aneurysms (IAs). This study aimed to explore miRNA levels in plasma exosomes of patients with IA to identify potential biomarkers that predict the development and progress of IA.

Methods: A total of 69 patients with IA and 30 healthy controls (HC) were recruited, among whom 30 had unruptured IA (UA), and 39 had ruptured IA (RA). The miRNA expression profiles of plasma exosomes in 12 IA patients (4 UA and 8 RA) and 4 HC were determined using next-generation sequencing. In addition, significantly differentially expressed miRNAs were further analyzed by Quantitative Real-Time PCR (qRT-PCR) in a validation cohort of 99 subjects.

Results: From the sequencing analysis, 181 miRNAs were identified to be differently ( p < 0.05) expressed. Of these, 9 miRNAs were up-regulated, and 20 were down-regulated in patients with UA compared with HC. Also, 21 were up-regulated, and 10 were down-regulated in patients with RA compared with HC. In addition, compared with UA, 92 miRNAs were up-regulated in RA, whereas 29 were down-regulated. Furthermore, qRT-PCR analysis confirmed that miR-145-5p and miR-29a-3p were up-regulated in IA samples. To distinguish IA patients from controls, the area under the receiver operating characteristic curve was 0.791 for miR-29a-3p, while that of miRNA-145-5p was 0.773 in terms of discriminating whether the aneurysm was ruptured.

Conclusions: Circulating exosomal miRNAs can serve as biomarkers of the development and progression of IA.