CBMT-19. RNU6-1 ANALYSED IN EXOSOMES FROM SERA AS A NOVEL DIFFERENTIAL BIOMARKER FOR GBM VS NON-NEOPLASTIC BRAIN LESIONS AND NSCPL

The identification of circulating biomarkers by non-invasive methods would be helpful for glioma detection and response assessment. Strong evidences have shown that GBM cells release microvesicles containing proteins and RNA. We have previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to control samples; therefore it could serve as a non-invasive diagnostic biomarker for GBM. In this study, we set to investigate the role of RNU6-1 as a differential biomarker of GBM versus other brain diseases with similar radiological features. RNU6-1 expression was analysed by digital droplet PCR (ddPCR) in circulating exosomes from serum samples of GBM patients (n=18), healthy controls (n=28), and patients with different brain lesions: subacute stroke (n=30), acute-subacute haemorrhage (n=29), acute demyelinating lesions (n=19), brain metastases (n=21) and Primary CNS Lymphomas (PCNSL) (n=12). We observed that the expression of RNU6-1 was significantly higher in GBM patients (412 ± 550.48 copies/20µL) than in healthy controls (150 ± 224.35 copies/20µL; p=0.039) validating our preceding results. Furthermore, RNU6-1 levels were increased in exosomes from GBM patients than in exosomes from patients with non-neoplastic lesions (stroke [223 ± 709.8 copies/20µL; p=0,067], haemorrhage [127 ± 198.7 copies/20µL; p=0.010], demyelinating lesions [111.5 ± 250.35 copies/20µL; p=0.019]) and PCNSL [18.15 ± 245.7 copies/20µL; p=0.004]). Contrary, RNU6-1 levels were similar between brain metastases and GBM patients [325 ± 632 copies/20µL; p=0.573]. In addition, assessing RNU6-1 as a predictive marker of GBM by ROC curves analysis, we demonstrated that RNU6-1 was a robust diagnostic biomarker of GBM compared to subacute stroke [AUC=0.659; p=0.004], acute/subacute haemorrhage [AUC=0.724; p=0.006], acute demyelinating lesions [AUC=0.728; p=0.011] and PCNSL [AUC=0.814; p<0.001]; in contrast, it did not allow differentiating GBM from brain metastases [AUC=0.552; p=0.575]. Our data indicate that RNU6-1 from circulating exosomes could serve as a differential biomarker for GBM versus non-neoplastic brain lesions and PCNSL, therefore, be used as a non-invasive method for GBM diagnosis.