Exploring CSF microRNA signatures as diagnostic biomarkers in adult-type diffuse gliomas

Area of Science:

• Neuro-oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Isocitrate dehydrogenase (IDH) mutations define molecular subtypes of diffuse gliomas (DG).
• Extracellular vesicle-derived microRNAs (EV-miRNAs) in cerebrospinal fluid (CSF) may serve as minimally invasive biomarkers for DG.

Purpose of the Study:

• To identify and validate CSF EV-miRNAs as diagnostic and prognostic biomarkers for DG molecular subtypes.
• To investigate the potential of EV-miRNAs in differentiating IDH-wildtype from IDH-mutant gliomas and glioblastoma (GBM) from controls.

Main Methods:

• miRNA-sequencing (miRNA-seq) and quantitative real-time PCR (qRT-PCR) were used to analyze EV-miRNAs in CSF samples.
• Multivariable logistic regression (MLR) identified differentially expressed microRNAs (DE-miRNAs) and assessed their diagnostic accuracy (AUC).
• Ingenuity Pathway Analysis (IPA) and DAVID were employed for pathway and disease enrichment analysis of miRNA targets.

Main Results:

• EV-miR-21-5p differentiated GBM from controls (AUC=0.84) and IDH-mutant gliomas from controls (AUC=0.93).
• A panel of five miRNAs (miR-150-5p, miR-142-3p, miR-19b-3p, miR-99a-5p, miR-27b-3p) accurately distinguished IDH-wildtype from IDH-mutant gliomas (AUC=1.00).
• Nine specific miRNAs significantly differentiated GBM from controls (AUC=1.00), and miR-142-3p alone discriminated IDH-mutant gliomas from controls (AUC=1.00).

Conclusions:

• CSF-derived EV-miRNAs can serve as robust, minimally invasive biomarkers for the molecular classification of diffuse gliomas.
• The identified miRNA panels demonstrate high accuracy in distinguishing between different glioma subtypes and non-tumor states.
• These findings support the clinical utility of EV-miRNAs for non-invasive glioma diagnosis and molecular subtyping.