Diagnostic acuuracy of cerebrospinal fluid and serum-isolated exosomes for glioblastoma: a systematic review and meta-analysis

Abstract

Glioblastoma (GBM) is the most malignant glioma cancer with a high morbidity and mortality worldwide. Unfortunately, a routine method is not available for screening or preoperative early detection of GBM. However, early detection in a none-invasive or minimally invasive method could be beneficial and increase the survival rate. In this systematic review and meta-analysis, we aimed to examine the diagnostic accuracy of exosomal RNAs that were extracted from patients' CSF or serum for GBM diagnosis. We searched Web of Science, Scopus, PubMed (including Medline), Embase and ProQuest (as databases for grey literature) up to December 2019; we also performed backward and forward reference checking of included and relevant studies. Finally, included studies were assessed with QUADAS-2 checklist and their data extracted. We carried out a meta-analysis of included study, regarding to the diagnostic meta-analysis guidelines for obtaining pooled accuracy estimates. In addition, sensitivity analysis and meta-regression were also conducted. We retrived 1730 records from databases, nine of them included in systematic review and qualitative synthesis. Six studies were considered to statistical analysis and performed diagnostic meta-analysis. Our results suggested that the pooled sensitivity and specificity of exosomal biomarkers for GBM were 0.76 and 0.80, respectively. In addition, the pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.7, 0.30 and 12, respectively. The overall area under the curve (AUC) of exosomal biomarkers for GBM diagnosis was found to be 0.85. According to our results, the value of 0.85 for AUC, suggesting that exosomal biomarkers might serve as a high potential and noninvasive diagnostic tool for GBM. JP, Heese O, Reifenberger G et al: Long-term survival with glioblastoma multiforme. Brain : a journal of neurology 2007, 130(Pt 10):2596-2606. 3. Kim S-S, Harford JB, Pirollo KF, Chang EH: Effective treatment of glioblastoma requires crossing the blood-brain barrier and targeting tumors including cancer stem cells: the promise of nanomedicine. Biochemical and biophysical research communications 2015, 468(3):485-489. 4. targeting and microenvironment-responsive nanoparticles for gene delivery. Biomaterials 2013, 34(21):5294-5302. 5. Emery JD, Shaw K, Williams B, Mazza D, Fallon-Ferguson J, Varlow M, Trevena LJ: The role of primary care in early detection and follow-up of cancer. Nature Reviews Clinical Oncology 2014, 11(1):38-48. 6. Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A, Kuker H, Sion-Vardy N, Tobar A, Kharenko O: MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain pathology 2009, 19(3):375-383. 7. Schwartz SA, Weil RJ, Thompson RC, Shyr Y, Moore JH, Toms SA, Johnson MD, Caprioli RM: Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. Cance...