title: A miRNA signature for defining aggressive phenotype and prognosis in gliomas.
abstract: Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA (miRNA) profile of 8 WHO grade II gliomas and 24 higher grade tumours (2 WHO grade III and 22 glioblastomas) by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method (RT-qPCR) with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas (TCGA) datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients' groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme (GBM) and Lower Grade Glioma (LGG) datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. 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 HR 1.18, 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.
authors.affiliation: Laboratory of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Barbano
authors.affiliation: Laboratory of Genetics, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.affiliation: Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasculli
authors.affiliation: LTTA, Department of Morphology, Surgery and Experimental Medicine, Human Anatomy Branch, University of Ferrara, Ferrara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Galasso
authors.affiliation: LTTA, Department of Morphology, Surgery and Experimental Medicine, Human Anatomy Branch, University of Ferrara, Ferrara, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.affiliation: Department of Neurosurgery, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: D'Angelo
authors.affiliation: Department of Neurosurgery, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Icolaro
authors.affiliation: Laboratory of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Michelina
authors.initials: M
authors.lastname: Coco
authors.affiliation: Department of Pathology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Dimitri
authors.affiliation: Department of Pathology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
authors.affiliation: Unit of Biostatistics, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Department of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Vanna Maria
authors.initials: VM
authors.lastname: Valori
authors.affiliation: Department of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.affiliation: Laboratory of Genetics, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.affiliation: Laboratory of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy; CIR Laboratory for Molecular Medicine and Biotechnology, University Campus Biomedico, Rome, Italy.
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Fazio
authors.affiliation: Laboratory of Oncology, "IRCCS Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Parrella
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs