Circulating microRNAs in patients with intracranial aneurysms.

Abstract

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 p1.2 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.