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
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
Department of Neurosciences, Neurosurgery Unit, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
Biomark Res. 2022 Jun 17;10(1):44. doi: 10.1186/s40364-022-00389-x.
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.
We identified and validated supratentorial incompletey resected pLGG-specific microRNAs in independent cohorts from four European Pediatric Neuro-Oncology Centres.
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.
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.
小儿低级别胶质瘤（pLGGs），尤其是幕上未完全切除的肿瘤，术后可能会进展。然而，迄今为止，尚无用于预测进展的生物标志物。在此，我们旨在识别pLGG特异性的微小RNA特征，并评估其作为预后工具的价值。
我们在来自四个欧洲儿科神经肿瘤中心的独立队列中识别并验证了幕上未完全切除的pLGG特异性微小RNA。
这些微小RNA在区分有或无进展的患者方面显示出高准确性。具体而言，疾病进展的幕上未完全切除的pLGGs与无进展的肿瘤相比，miR-1248水平显著更高，同时miR-376a-3p和miR-888-5p水平更低。据报道，miR-1248具有显著的（p < 0.001）预后性能，曲线下面积（AUC）为1.00。我们还强调了miR-1248在胶质瘤肿瘤中的关键致癌作用。事实上，高miR-1248水平使其已验证的靶基因（CDKN1A（p21）/FRK/SPOP/VHL/MTAP）维持在低水平，从而维持致癌途径的激活。
总之，我们提供了一种新型分子生物标志物，能够成功识别与疾病进展相关的pLGG患者，这可以支持临床医生制定决策策略，推动个性化医疗。
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