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Published on: January 22, 2014
Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture
Manjunath Supriya1, Rita Christopher2, Bhagavatula Indira Devi3
1Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences(NIMHANS), Bengaluru, 560029, India.
Introduction:
Diagnosis of the rupture of an intracranial aneurysm (IA) relies on sophisticated neuro-imaging studies, and molecular biomarkers to identify an IA or predict its rupture are still unavailable.
Objective:
Our objective was to determine the plasma microRNA (miRNA) expression profile in patients with ruptured IA presenting as aneurysmal subarachnoid hemorrhage (aSAH) and identify potential biomarkers of aneurysmal rupture.
Methods:
Plasma miRNA profiling was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) in 20 patients with aSAH and 20 age- and sex-matched healthy controls. Eight differentially expressed miRNAs were validated by qPCR in a larger cohort of 88 patients with aSAH and 110 healthy controls. A receiver operating characteristic (ROC) curve was constructed to evaluate the overall performance of the miRNA-based assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to determine the potential pathway of miRNA-target genes.
Results:
The miRNA profiles were clearly distinct in patients compared with controls. Validation studies showed that three upregulated miRNAs (miR-15a-5p, miR-34a-5p, miR-374a-5p) and five downregulated miRNAs (miR-146a-5p, miR-376c-3p, miR-18b-5p, miR-24-3p, miR-27b-3p) could distinguish patients with aSAH from healthy controls with high predicted probability (0.865 and 0.995, respectively). Further, the expression levels of the eight candidate miRNAs were significantly dysregulated only in aSAH cases and not in patients with SAH due to other causes. Plasma miR-146a-5p and miR-27b-3p were associated with clinical outcomes in patients with aSAH. Functional analysis of the eight differentially expressed miRNA showed that the target genes involved in signaling pathways were related to inflammation.
Conclusions:
Our study determined the plasma miRNA signature of ruptured IAs and identified eight candidate miRNAs that could be useful biomarkers for this condition. We hypothesize that these differentially expressed miRNAs may play pivotal roles in IA pathology.
Insights
Researchers identified eight plasma microRNAs (miRNAs) that can serve as biomarkers for ruptured intracranial aneurysms (IAs). These specific miRNA signatures distinguish patients with aneurysmal subarachnoid hemorrhage (aSAH) from healthy individuals, offering potential diagnostic tools.
Area of Science:
- Biochemistry
- Genetics
- Neuroscience
Background:
- Diagnosis of ruptured intracranial aneurysms (IAs) relies on advanced neuro-imaging.
- Currently, no molecular biomarkers exist to identify IAs or predict their rupture.
Purpose of the Study:
- To determine plasma microRNA (miRNA) expression profiles in patients with aneurysmal subarachnoid hemorrhage (aSAH).
- To identify potential miRNA biomarkers for aneurysmal rupture.
Main Methods:
- Plasma miRNA profiling using quantitative real-time polymerase chain reaction (qRT-PCR) in aSAH patients and healthy controls.
- Validation of differentially expressed miRNAs in a larger cohort.
- Receiver operating characteristic (ROC) curve analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
Main Results:
- Distinct miRNA profiles were observed between aSAH patients and controls.
- Eight miRNAs (3 upregulated, 5 downregulated) differentiated aSAH patients from controls with high accuracy.
- These miRNAs were specifically dysregulated in aSAH, not in other types of subarachnoid hemorrhage.
- Two miRNAs, miR-146a-5p and miR-27b-3p, correlated with clinical outcomes.
- Target genes of these miRNAs are involved in inflammation-related signaling pathways.
Conclusions:
- A plasma miRNA signature for ruptured IAs was identified.
- Eight candidate miRNAs show potential as biomarkers for ruptured IAs.
- These differentially expressed miRNAs may play a significant role in IA pathology.
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