Circulating microRNAs Serve as Novel Biological Markers for Intracranial Aneurysms

BACKGROUND Biological markers that can be used to predict the risk of intracranial aneurysms (IAs) are not available. METHODS AND RESULTS To clarify whether circulating microRNAs could be used as biomarkers for IA, we carried out microarray assays in a screening cohort of 40 IA patients (20 unruptured and 20 ruptured) and 20 healthy volunteers. We identified 20 microRNAs that were unanimously changed in both ruptured and unruptured patients. We confirmed 60% of these changed microRNAs by a separate microarray test with an independent validation cohort (n=143 including 93 IA patients). To identify potential biomarkers, we combined the 2 cohorts and performed quantitative real-time polymerase chain reactions for selected target microRNAs. Logistic regression analysis demonstrated that miR-16 and miR-25 were independent factors for IA occurrence (P<0.001). After controlling for age, sex, smoking, and history of hypertension, the contributions of miR-16 and miR-25 were still highly significant (P<0.001). The adjusted odds ratio values for miR-16 and miR-25 were 1.52 (95% CI 1.31 to 1.77) and 1.53 (1.30 to 1.79). Combining both miR-16 and miR-25 in a single model did not improve the performance of risk association. CONCLUSIONS Our data suggest that circulating miRNAs may be novel biological markers that are useful in assessing the likelihood of IA occurrence.