MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression

Giuseppina Catanzaro , Zein Mersini Besharat , Andrea Carai , Natalie Jäger , Elena Splendiani , Carole Colin (1) , Agnese Po , Martina Chiacchiarini , Anna Citarella , Francesca Gianno , Antonella Cacchione , Evelina Miele , Francesca Diomedi Camassei , Marco Gessi , Luca Massimi , Franco Locatelli , David Jones , Dominique Figarella‑branger (1) , Stefan Pfister , Angela Mastronuzzi , Felice Giangaspero , Elisabetta Ferretti

1 INP - Institut de neurophysiopathologie

Background Pediatric low-grade gliomas (pLGGs), particularly incompletely resected supratentorial tumours, can undergo progression after surgery. However to date, there are no predictive biomarkers for progression. Here, we aimed to identify pLGG-specific microRNA signatures and evaluate their value as a prognostic tool. Methods We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres. Results These microRNAs demonstrated high accuracy in differentiating patients with or without progression. Specifically, incompletely resected supratentorial pLGGs with disease progression showed significantly higher miR-1248 combined with lower miR-376a-3p and miR-888-5p levels than tumours without progression. A significant ( p < 0.001) prognostic performance for miR-1248 was reported with an area under the curve (AUC) of 1.00. We also highlighted a critical oncogenic role for miR-1248 in gliomas tumours. Indeed, high miR-1248 levels maintain low its validated target genes (CDKN1A (p21)/FRK/SPOP/VHL/MTAP) and consequently sustain the activation of oncogenic pathways. Conclusions Altogether, we provide a novel molecular biomarker able to successfully identify pLGG patients associated with disease progression that could support the clinicians in the decision-making strategy, advancing personalized medicine.

Mots clés: Pediatric low-grade gliomas; miR-1248; Prognostic biomarker; Tumour progression; Risk stratification; Personalized medicine

Domaines: Sciences du Vivant [q-bio]; Cancer

Giuseppina Catanzaro, Zein Mersini Besharat, Andrea Carai, Natalie Jäger, Elena Splendiani, et al.. MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression. Biomarker Research, 2022, 10 (1), pp.44. ⟨10.1186/s40364-022-00389-x⟩. ⟨hal-03982375⟩