Jamie Weihe

Introduction Glioblastoma (GB) is the most malignant primary brain tumor¹, with an average survival rate of 12-15 months even with aggressive treatment.² Complicating treatment is a lack of timely and accurate diagnosis and sensitive therapeutic monitoring.³ Research points towards miRNAs as novel biomarkers that can help diagnose and type the stage of a patient’s GB, both before and after treatment.⁴ MiR-21 is an ideal candidate for a biomarker as it is upregulated in GB and is found circulating in CSF and serum in exosomes.³ Researchers see the potential for exosomal miR-21 to bridge the gap as a relatively non-invasive biomarker to lend earlier detection of tumor growth and an accurate prognosis based on glioma grade. Methods To elucidate the nature of exosomal miR-21 frequency in glioma development, one early team of researchers analyzed the miR-21 content in a panel of GB cell lines and compared the levels to those found in secreted cell line EVs.³ Another later study utilized lumbar puncture to collect CSF of recurrent GB patients with subsequent centrifugation.  ROC analysis compared exosome levels in glioma and non-glioma patients, as well as lower and higher grade glioma patients, giving ROC values of 0.927 and 0.872.⁵ Other research emphasized the prognostic value of miR-21 by extracting exosomes from serum of patients with high and low grade primary gliomas, both before and after surgical resection.⁶ Results Research has established the predictive value of miR-21 in early diagnosis of GB. The positive correlation between miR-21 and GB has been shown via panels of GB cell lines that correlate with the levels found in EVs secreted by the GB cells, ³ and in CSF from GB patients compared to a control group.⁵ Exosomal miR-21 is significantly upregulated in patients before and after successful surgical resection, which indicates a marker to determine the effectiveness of surgical treatment.⁶ Conclusion Research strongly supports exosomal miR-21 as a relatively non-invasive biomarker for the early and accurate detection of GB as well as a prognostic indicator in early and later stages of treatment. It serves the purpose of typing glioma grade so as to differentiate GB from less aggressive tumor types, and can indicate recurrence after surgical resection. Both exosomal and serum detection of exosomes carrying miR-21 may be of use as a biomarker, and the techniques for detection are being refined in the literature.

1. Agnihotri S, Burrel KE, Wolf A, et al. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Archivum Immunologiae et Therapiae Experimentalis. 2013:61(1):25-41.
2. Cloughesy TF, Cavenee WK, and Mischel PS. Glioblastoma: from molecular pathology to targeted treatment. Annual Review of Pathology: Mechanisms of Disease. 2014:9:1-25.
3. Akers JC, Ramakrishnan V, Kim R, et al. “MiR-21 in the extracellular vesicles (EVs) of cerebrospinal fluid (CSF): a platform for glioblastoma biomarker development.” PLoS ONE. 2013:8(10):e78115-e78115.
4. Saadatpour L, Fadaee E, Fadaei S, et al. “Glioblastoma: exosome and microRNA as novel diagnosis biomarkers.” Cancer Gene Therapy 23.12 (2016):415-418.
5. Shi R, Wang P-Y, Li X-Y, et al. Exosomal levels of miRNA-21 from cerebrospinal fluids associated with poor prognosis and tumor recurrence of glioma patients. Oncotarget. 2015;6(29):26971-26981.
6. Santangelo A, Imbrucè P, Gardenghi B. et al. A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker. J Neurooncol. 2018;136(51).