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.

MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression / Catanzaro, Giuseppina; Besharat, Zein Mersini; Carai, Andrea; Jäger, Natalie; Splendiani, Elena; Colin, Carole; Po, Agnese; Chiacchiarini, Martina; Citarella, Anna; Gianno, Francesca; Cacchione, Antonella; Miele, Evelina; Diomedi Camassei, Francesca; Gessi, Marco; Massimi, Luca; Locatelli, Franco; Jones, David T W; Figarella-Branger, Dominique; Pfister, Stefan M; Mastronuzzi, Angela; Giangaspero, Felice; Ferretti, Elisabetta. - In: BIOMARKER RESEARCH. - ISSN 2050-7771. - 10:1(2022). [10.1186/s40364-022-00389-x]

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

Catanzaro, Giuseppina
Co-primo
;
Besharat, Zein Mersini
Co-primo
;
Splendiani, Elena;Po, Agnese;Chiacchiarini, Martina;Citarella, Anna;Gianno, Francesca;Cacchione, Antonella;Miele, Evelina;Locatelli, Franco;Mastronuzzi, Angela;Giangaspero, Felice
Penultimo
;
Ferretti, Elisabetta
Ultimo
2022

Abstract

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.
2022
pediatric low-grade gliomas; personalized medicine; prognostic biomarker; risk stratification; tumour progression; mir-1248
01 Pubblicazione su rivista::01a Articolo in rivista
MiR-1248: a new prognostic biomarker able to identify supratentorial hemispheric pediatric low-grade gliomas patients associated with progression / Catanzaro, Giuseppina; Besharat, Zein Mersini; Carai, Andrea; Jäger, Natalie; Splendiani, Elena; Colin, Carole; Po, Agnese; Chiacchiarini, Martina; Citarella, Anna; Gianno, Francesca; Cacchione, Antonella; Miele, Evelina; Diomedi Camassei, Francesca; Gessi, Marco; Massimi, Luca; Locatelli, Franco; Jones, David T W; Figarella-Branger, Dominique; Pfister, Stefan M; Mastronuzzi, Angela; Giangaspero, Felice; Ferretti, Elisabetta. - In: BIOMARKER RESEARCH. - ISSN 2050-7771. - 10:1(2022). [10.1186/s40364-022-00389-x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1649691
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