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Background <p>Intracranial aneurysms (IAs) pose a significant clinical threat due to their potential to rupture, often resulting in subarachnoid hemorrhage and high mortality. While imaging and computational models have improved aneurysm characterization, accurate rupture risk prediction remains elusive. MicroRNAs (miRNAs), which are short non-coding RNA molecules that modulate gene expression after transcription, have gained attention as promising, non-invasive biomarkers with the potential to detect molecular changes that occur prior to aneurysm rupture. This review synthesizes current evidence on miRNAs’ diagnostic and pathophysiological relevance in IA rupture risk assessment.</p> Methods <p>A scoping review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A systematic search of six databases (PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar) identified human studies comparing miRNA expression profiles in ruptured versus unruptured intracranial aneurysms using blood, serum, plasma, cerebrospinal fluid, or aneurysmal tissue. The search was performed from 2010 until March 2025. Eligible studies reported differential expressions or diagnostic performance metrics. Extracted data included study design, biological matrix, analytical techniques, evaluated miRNA targets, and correlation with rupture risk.</p> Results <p>A total of 21 studies were included. Upregulated miRNAs in ruptured intracranial aneurysms (IAs) included miR-29a, miR-574-5p, miR-151a-3p, and miR-652-3p, whereas miR-143, miR-145-5p, miR-21, and miR-125b-5p were commonly downregulated. These dysregulations were linked to extracellular matrix remodeling, vascular inflammation, and apoptosis. Diagnostic analyses identified strong discriminatory performance for plasma miR-574-5p, miR-151a-3p, and miR-652-3p (AUCs 0.92–0.99). Additional candidates such as miR-126 (AUC 0.897) and circulating miR-16/25 (AUCs 0.85–0.88) also showed high accuracy, while tissue-based studies revealed that downregulation of miR-125b-5p, miR-143-3p, and miR-199a-5p correlated with poor WFNS grade. Overall, selected miRNAs, most notably miR-125b-5p, miR-574-5p, miR-29a, miR-126, and miR-16/25, emerged as promising minimally invasive biomarkers for rupture risk prediction.</p> Conclusions <p>Circulating and exosomal miRNAs offer a compelling non-invasive IA rupture risk stratification strategy. However, clinical translation demands standardized methodologies, larger cohorts, and imaging and computational tools.</p>

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Scoping review of MicroRNAs as biomarkers for rupture risk prediction in intracranial aneurysms

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月24日

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  • Gustavo Adolfo Villegas-Gomez,
  • Nicolás Rincón-Arias,
  • Maria Alejandra Sierra,
  • Luisa F. Figueredo,
  • Juan F. Ramón,
  • Diego F. Gomez,
  • Fernando Hakim,
  • Pedro Andrade-Andrade,
  • Edgar G. Ordóñez-Rubiano

摘要

Background

Intracranial aneurysms (IAs) pose a significant clinical threat due to their potential to rupture, often resulting in subarachnoid hemorrhage and high mortality. While imaging and computational models have improved aneurysm characterization, accurate rupture risk prediction remains elusive. MicroRNAs (miRNAs), which are short non-coding RNA molecules that modulate gene expression after transcription, have gained attention as promising, non-invasive biomarkers with the potential to detect molecular changes that occur prior to aneurysm rupture. This review synthesizes current evidence on miRNAs’ diagnostic and pathophysiological relevance in IA rupture risk assessment.

Methods

A scoping review was conducted in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A systematic search of six databases (PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar) identified human studies comparing miRNA expression profiles in ruptured versus unruptured intracranial aneurysms using blood, serum, plasma, cerebrospinal fluid, or aneurysmal tissue. The search was performed from 2010 until March 2025. Eligible studies reported differential expressions or diagnostic performance metrics. Extracted data included study design, biological matrix, analytical techniques, evaluated miRNA targets, and correlation with rupture risk.

Results

A total of 21 studies were included. Upregulated miRNAs in ruptured intracranial aneurysms (IAs) included miR-29a, miR-574-5p, miR-151a-3p, and miR-652-3p, whereas miR-143, miR-145-5p, miR-21, and miR-125b-5p were commonly downregulated. These dysregulations were linked to extracellular matrix remodeling, vascular inflammation, and apoptosis. Diagnostic analyses identified strong discriminatory performance for plasma miR-574-5p, miR-151a-3p, and miR-652-3p (AUCs 0.92–0.99). Additional candidates such as miR-126 (AUC 0.897) and circulating miR-16/25 (AUCs 0.85–0.88) also showed high accuracy, while tissue-based studies revealed that downregulation of miR-125b-5p, miR-143-3p, and miR-199a-5p correlated with poor WFNS grade. Overall, selected miRNAs, most notably miR-125b-5p, miR-574-5p, miR-29a, miR-126, and miR-16/25, emerged as promising minimally invasive biomarkers for rupture risk prediction.

Conclusions

Circulating and exosomal miRNAs offer a compelling non-invasive IA rupture risk stratification strategy. However, clinical translation demands standardized methodologies, larger cohorts, and imaging and computational tools.