Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation

Aibaidula, Abudumijiti; Gharibi Loron, Ali; Bouchal, Samantha M.; Bauman, Megan M. J.; You, Hyo Bin; Lucien, Fabrice; Parney, Ian F.

doi:10.3390/ijms262311686

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Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation

by

Abudumijiti Aibaidula

^1,2,

Ali Gharibi Loron

²

,

Samantha M. Bouchal

^1,2,3,

Megan M. J. Bauman

^2,3,

Hyo Bin You

^2,3

,

Fabrice Lucien

^4,5

and

Ian F. Parney

^2,4,*

¹

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55901, USA

²

Department of Neurological Surgery, Mayo Clinic, Rochester, MN 55901, USA

³

Mayo Clinic Aix School of Medicine, Mayo Clinic, Rochester, MN 55901, USA

⁴

Department of Immunology, Mayo Clinic, Rochester, MN 55901, USA

⁵

Department of Urology, Mayo Clinic, Rochester, MN 55901, USA

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(23), 11686; https://doi.org/10.3390/ijms262311686

Submission received: 3 November 2025 / Revised: 26 November 2025 / Accepted: 28 November 2025 / Published: 2 December 2025

(This article belongs to the Section Molecular Oncology)

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Abstract

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, has a median survival of 14–15 months despite aggressive treatment. Monitoring relies on MRI, but differentiating tumor progression from pseudo-progression or radiation necrosis remains difficult. Plasma extracellular vesicles (EVs) are emerging as promising non-invasive biomarkers due to their molecular cargos and accessibility. This review evaluates studies that specifically isolated plasma EVs for molecular profiling in GBM diagnosis and monitoring. Biomarkers (miRNA, RNA, DNA, proteins), EV characterization methods, and advancements in enriching tumor-derived EV subpopulations and assessing their diagnostic and prognostic potential are highlighted. Plasma EVs carry diverse cargos, including miRNAs (e.g., miR-21, miR-15b-3p), mRNAs (e.g., EGFRvIII), circRNAs, and proteins (e.g., CD44, GFAP). Composite molecular signatures have achieved sensitivities of 87–100% and specificities of 73–100% for GBM diagnosis. Tumor-derived EVs, enriched using techniques like SEC-CD44 immunoprecipitation, microfluidic platforms, or 5-ALA-induced PpIX fluorescence, enhance biomarker detection. Non-tumor-derived EVs may also reflect GBM’s systemic effects. Challenges include EV heterogeneity, non-EV contamination, and variable biomarker expression across studies. Plasma-EV-based liquid biopsies offer significant potential for GBM monitoring, with advanced enrichment methods improving tumor-specific biomarker detection. Standardizing isolation protocols and validating biomarkers in larger cohorts are critical for clinical translation.

Keywords: extracellular vesicles; glioblastoma; liquid biopsy; plasma biomarkers

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MDPI and ACS Style

Aibaidula, A.; Gharibi Loron, A.; Bouchal, S.M.; Bauman, M.M.J.; You, H.B.; Lucien, F.; Parney, I.F. Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation. Int. J. Mol. Sci. 2025, 26, 11686. https://doi.org/10.3390/ijms262311686

AMA Style

Aibaidula A, Gharibi Loron A, Bouchal SM, Bauman MMJ, You HB, Lucien F, Parney IF. Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation. International Journal of Molecular Sciences. 2025; 26(23):11686. https://doi.org/10.3390/ijms262311686

Chicago/Turabian Style

Aibaidula, Abudumijiti, Ali Gharibi Loron, Samantha M. Bouchal, Megan M. J. Bauman, Hyo Bin You, Fabrice Lucien, and Ian F. Parney. 2025. "Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation" International Journal of Molecular Sciences 26, no. 23: 11686. https://doi.org/10.3390/ijms262311686

APA Style

Aibaidula, A., Gharibi Loron, A., Bouchal, S. M., Bauman, M. M. J., You, H. B., Lucien, F., & Parney, I. F. (2025). Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation. International Journal of Molecular Sciences, 26(23), 11686. https://doi.org/10.3390/ijms262311686

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Plasma Extracellular Vesicles as Liquid Biopsies for Glioblastoma: Biomarkers, Subpopulation Enrichment, and Clinical Translation

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