Systems biology in unruptured intracranial aneurysm: a metabolomics study in serum for the detection of biomarkers

Intracranial aneurysm (IA) is a common devastating condition occurs in up to 6 % of the population. It is asymptomatic but potentially fatal because of the progressive enlargement and rupturing leads to subarachnoid hemorrhage. Early diagnosis of IA is more valuable before it ruptures and hemorrhage. The diagnosis of IA is usually carried out using computerized tomography or magnetic resonance imaging. However, there is no biochemical test or a marker available for diagnosis. Serum metabolites were analyzed from normal and unruptured intracranial aneurysms patients (UIA) by NMR spectroscopy to identify the presence of serum markers, which could provide a clue for diagnosis and altered metabolic pathways in UIA condition. Analysis of proton spectra revealed significant perturbations in 20 serum metabolites in UIA. Multivariate analysis showed a distinct separation of normal from UIA based on 17 most contributing metabolites, and the scoring algorithm determines the perturbed metabolic pathways in UIA (urea cycle, citric acid cycle and ammonia recycling). Also, the gene expression analysis shows the significant (p ≤ 0.05) change in ARG, CPS1 and OTC genes leading to dysregulation in the urea cycle. Further, estimation of urea showed a significant increase in serum urea, which provides the prospect of rapid diagnosis. Overall, this study demonstrates the promise of developing biomarkers for the diagnosis of UIA from serum. In addition, the implementation of systems biological approach in metabolomic context gained an understanding about UIA that reflects the numerous metabolic pathways identified to be affected in disease condition.