
Circulating microRNAs in patients with intracranial aneurysms
Author(s) -
John A. L. Meeuwsen,
Femke N.G. van ‘t Hof,
Wouter van Rheenen,
Gabriël J.E. Rinkel,
Jan H. Veldink,
Ynte M. Ruigrok
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0176558
Subject(s) - microrna , medicine , cardiology , biology , genetics , gene
Introduction We compared circulating microRNA (miRNA) levels in plasma of patients with intracranial aneurysms (IA) to those of controls as a first step towards finding potential biomarkers for individuals at high risk of IA development and its subsequent rupture. Patients and methods Using a PCR array we measured 370 miRNAs in plasma of 15 patients with prior aneurysmal subarachnoid hemorrhage (aSAH), of whom 11 had an additional unruptured IA (UIA), and of 15 controls. MiRNAs with a difference in levels with an absolute fold change (FC) > 1.2 and p<0.01 were further tested using real-time (RT) PCR in an additional independent set of 15 aSAH patients, 15 untreated UIA patients and 15 controls for replication (absolute FC >1.2 and p<0.05). We used receiver operating characteristic (ROC) curves to illustrate the diagnostic potential of these miRNAs. Results Three of five miRNAs with a difference in levels in the PCR array study were replicated with miRNA-183-5p decreased in all patients (FC = -2.2, p = 1.7x10 -3 ), miRNA-200a-3p increased in aSAH patients (FC = 1.8, p = 2.8x10 -2 ) and miRNA-let7b-5p decreased in UIA patients (FC = -1.7, p = 1.27x10 -3 ) as compared to controls. In distinguishing aSAH patients from controls, the area under the ROC curve (AUC) was 0.80 (95% confidence interval (95% CI) 0.63–0.97) for miRNA-183-5p, and 0.74 (95% CI 0.55–0.94) for miRNA-200a-3p. In distinguishing untreated UIA patients from controls, AUC was 0.83 (95% CI 0.69–0.98) for miRNA-183-5p and 0.92 (95% CI 0.81–1) for miRNA-let-7b. Discussion/Conclusions We identified three specific circulating miRNAs that are able to discriminate between IA patients and controls. Follow-up studies should assess if these miRNAs may be used biomarkers for identifying individuals at high risk of IA development and its subsequent rupture.