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Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture.
Mol Diagn Ther. 2020 06; 24(3):351-364.MD

Abstract

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.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Supriya M
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences(NIMHANS), Bengaluru, 560029, India.
Christopher R
Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences(NIMHANS), Bengaluru, 560029, India. rita@nimhans.ac.in.
Indira Devi B
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, 560029, India.
Bhat DI
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, 560029, India.
Shukla D
Department of Neurosurgery, National Institute of Mental Health and Neuro Sciences, Bengaluru, 560029, India.

MeSH

AdultAgedAneurysm, RupturedBiomarkersCirculating MicroRNAComputational BiologyDisease ManagementDisease SusceptibilityFemaleGene Expression ProfilingGene OntologyHumansIntracranial AneurysmMaleMicroRNAsMiddle AgedMolecular Sequence AnnotationRNA InterferenceROC CurveReal-Time Polymerase Chain ReactionReproducibility of ResultsSensitivity and SpecificitySubarachnoid Hemorrhage

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32323261

Citation

Supriya, Manjunath, et al. "Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture." Molecular Diagnosis & Therapy, vol. 24, no. 3, 2020, pp. 351-364.
Supriya M, Christopher R, Indira Devi B, et al. Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture. Mol Diagn Ther. 2020;24(3):351-364.
Supriya, M., Christopher, R., Indira Devi, B., Bhat, D. I., & Shukla, D. (2020). Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture. Molecular Diagnosis & Therapy, 24(3), 351-364. https://doi.org/10.1007/s40291-020-00465-8
Supriya M, et al. Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture. Mol Diagn Ther. 2020;24(3):351-364. PubMed PMID: 32323261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating MicroRNAs as Potential Molecular Biomarkers for Intracranial Aneurysmal Rupture. AU - Supriya,Manjunath, AU - Christopher,Rita, AU - Indira Devi,Bhagavatula, AU - Bhat,Dhananjaya Ishwar, AU - Shukla,Dhaval, PY - 2020/4/24/pubmed PY - 2021/6/2/medline PY - 2020/4/24/entrez SP - 351 EP - 364 JF - Molecular diagnosis & therapy JO - Mol Diagn Ther VL - 24 IS - 3 N2 - 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. SN - 1179-2000 UR - https://www.unboundmedicine.com/medline/citation/32323261/Circulating_MicroRNAs_as_Potential_Molecular_Biomarkers_for_Intracranial_Aneurysmal_Rupture_ DB - PRIME DP - Unbound Medicine ER -