Circulating miRNAs for glioblastoma monitoring: from biofluid to clinical decision

Gliomas, particularly glioblastoma (GBM), remain highly lethal brain tumors with limited treatments. MRI-based monitoring lacks specificity in distinguishing progression from treatment effects. Circulating microRNAs (miRNAs), small non-coding RNAs involved in tumor biology, show promise as liquid biopsy biomarkers. We searched PubMed, Embase, Scopus, and Web of Science for clinical studies investigating circulating miRNAs as diagnostic, prognostic, or predictive biomarkers in glioma, across plasma, serum, and cerebrospinal fluid (CSF). Oncogenic miRNAs (oncomiRs) such as miR-21, miR-10b, miR-182, and miR-210 were consistently upregulated in glioma patients, whereas tumor suppressors including miR-124, miR-128, miR-137, and miR-181 family members were downregulated. Prognostically, elevated miR-21, miR-222, and miR-196b correlated with poor survival, while reduced miR-181d, miR-100, and miR-145 predicted worse outcomes. Composite signatures, particularly exosomal or CSF-derived panels, outperformed single markers. Dynamic changes in miR-21, miR-222, and miR-210 reflected treatment response or progression, with exosomal miR-1238 emerging as a marker of temozolomide resistance. Longitudinal serum levels of miR-223 and miR-320e correlated with MRI tumor volume and distinguished true progression from pseudo-progression. Circulating miRNAs show strong potential as minimally invasive biomarkers for glioma management, but clinical translation remains limited by technical and biological variability and lack of validation. Advances in biosensors, multi-omics, and standardization are key to clinical integration.