Circulating microRNA profiling in diffuse intrinsic pontine gliomas

Diffuse midline glioma (DMG) identifies gliomas originating in the thalami, brainstem, cerebellum and spine. Within this entity, tumours that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), have a rapid onset and devastating neurological symptoms. Radiotherapy is the only intervention that is able to modify the disease course, albeit not in a curative way. In recent years, liquid biopsies have represented the next step in clinical diagnostics due to their easily accessible nature. The purpose of this study is to profile circulating miRNA expression to disclose a potential prognostic signature with clinical impact. Blood samples were collected at the baseline prior to treatment, kept at 4 C for 30 minutes and processed within 1 h after collection by centrifugation at 1600 x g at 4 C for 10 min. Serum was aliquoted in vials and stored at -80 C. The miRNA expression was profiled using the miRNA microarray (Agilent) designed on miRBase 19.0; 2006 miRNAs were profiled in serum specimens from 47 patients enrolled in two clinical studies combining nimotuzumab with concomitant radiation and vinorelbine. Cases were divided in a training set (n=23) and an independent validation set (n=24). Having progression free survival as endpoint, a semi supervised learning approach was applied to disclose a prognostic signature.