期刊
PHARMACEUTICALS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ph14070618
关键词
glioblastoma multiforme; circRNAs; extracellular vesicles; diagnostic biomarkers
资金
- Lega Italiana per la Lotta contro i Tumori (LILT)
- PIAno di inCEntivi per la RIcerca (PIA.CE.RI.) di Ateneo 2020/2022-linea di intervento 3, STARTING GRANT (Project EPIGLI)
- Fondi di ateneo 2020/2022, Universita di Catania, linea Open Access, from the University of Catania
The study suggests that sEV-derived circSMARCA5 and circHIPK3 are potential diagnostic biomarkers for GBM, especially when combined with preoperative NLR, PLR, and LMR to improve diagnostic accuracy.
Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic biomarkers for GBM diagnosis. EVs were isolated by size exclusion chromatography from sera of 23 GBM and 5 grade 3 glioma (GIII) patients, and 10 unaffected controls (UC). The expression of two candidate circRNAs (circSMARCA5 and circHIPK3) was assayed by droplet digital PCR. CircSMARCA5 and circHIPK3 were significantly less abundant in sEVs from GBM patients with respect to UC (fold-change (FC) of -2.15 and -1.92, respectively) and GIII (FC of -1.75 and -1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on the expression of sEV-derived circSMARCA5 and circHIPK3, allowed us to distinguish GBM from UC (area under the curve (AUC) 0.823 (0.667-0.979) and 0.855 (0.704 to 1.000), with a 95% confidence interval (CI), respectively). Multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with preoperative neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) and lymphocyte to monocyte (LMR) ratios, three known diagnostic and prognostic GBM markers, allowed an improvement in the GBM diagnostic accuracy (AUC 0.901 (0.7912 to 1.000), 95% CI). Our data suggest sEV-derived circSMARCA5 and circHIPK3 as good diagnostic biomarkers for GBM, especially when associated with preoperative NLR, PLR and LMR.
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