Identification of miR21 and miR210 as biomarkers of aggressive clinical behaviour in glioblastoma.
Raffaela Barbano, Orazio Palumbo, Barbara Pasculli, Marco Galasso, Stefano Volinia Massimiliano Copetti, Vincenzo D’Angelo, Nadia Icolaro, Paolo Graziano, Massimiliano Copetti, Vanna Maria Valori, Evaristo Maiello, Massimo Carella, Vito Michele Fazio, Paola Parrella. IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo (FG) Italy , University of Ferrara, Ferrara, Italy
High grade gliomas account for approximately 70% of all primary malignant brain tumours and, despite improvements in the clinical care, they remain still associated with high mortality and morbidity underscoring the need for gaining new insights that could be translated into clinical advances. To date, common alterations in canonical central signaling pathways have been identified in gliomas but the mechanisms through which genomic and molecular abnormalities support their genesis and progression are still far from being decrypted. MicroRNAs (miRNAs) are small non-coding RNAs, of 18 to 25 nucleotides in length, involved in the post transcriptional regulation of gene expression. In the last few years, a number of studies, both in gliomas and other human malignancies, have revealed that miRNA expression signatures far surpass those of mRNAs in terms of defining tissue of origin, type and subtypes of cancer. Due to their tissue and disease specificity, miRNAs hold the potential to provide sensitive and specific biomarker panels for diagnostic and prognostic purposes. We performed the miRNA expression profiling on 32 gliomas (8 WHO II, 2 WHO III and 22 GBMs) and 4 commercially available normal brain tissues (NBT) by using the Affymetrix GeneChip® miRNA Array v.1.0. We identified 22 miRNAs distinguishing grade II from higher grade gliomas. 13 out of the 22 miRNAs were confirmed by RT-qPCR. The validation analysis on the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs (miR-21, miR-22, miR-210, miR-155, miR-223 and miR-219-2-3p). Moreover, in the GBM dataset, miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p=0.04, and HR1.18, p=0.029, respectively). Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.Format: Oral communication