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• W2416509920 abstract "// Maximilian Niyazi 1, 8, 9 , Adriana Pitea 2, 8 , Michel Mittelbronn 3 , Joachim Steinbach 4 , Carsten Sticht 5 , Franz Zehentmayr 1, 6 , Daniel Piehlmaier 2, 8 , Horst Zitzelsberger 2, 8 , Ute Ganswindt 1, 8 , Claus Rödel 7 , Kirsten Lauber 1, 8 , Claus Belka 1, 8, 9 , Kristian Unger 2, 8 1 Ludwig-Maximilians-University of Munich, Department of Radiation Oncology, Munich, Germany 2 Research Unit of Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany 3 Institute of Neurology (Edinger Institute), Goethe-University Frankfurt, Frankfurt/Main, Germany 4 Dr. Senckenbergisches Institut für Neuroonkologie, Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany 5 Zentrum für Medizinische Forschung, Medizinische Fakultät Mannheim, Mannheim, Germany 6 Department of Radiation Oncology, Paracelsus Medical University, Salzburg, Austria 7 Department of Radiation Oncology, University Hospital, Frankfurt, Germany 8 Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum München, Neuherberg, Germany 9 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany Correspondence to: Kristian Unger, email: unger@helmholtz-muenchen.de Keywords: glioblastoma, miRNA, signature Received: February 10, 2016     Accepted: May 22, 2016     Published: June 11, 2016 ABSTRACT Multimodal therapy of glioblastoma (GBM) reveals inter-individual variability in terms of treatment outcome. Here, we examined whether a miRNA signature can be defined for the a priori identification of patients with particularly poor prognosis. FFPE sections from 36 GBM patients along with overall survival follow-up were collected retrospectively and subjected to miRNA signature identification from microarray data. A risk score based on the expression of the signature miRNAs and cox-proportional hazard coefficients was calculated for each patient followed by validation in a matched GBM subset of TCGA. Genes potentially regulated by the signature miRNAs were identified by a correlation approach followed by pathway analysis. A prognostic 4-miRNA signature, independent of MGMT promoter methylation, age, and sex, was identified and a risk score was assigned to each patient that allowed defining two groups significantly differing in prognosis (p-value: 0.0001, median survival: 10.6 months and 15.1 months, hazard ratio = 3.8). The signature was technically validated by qRT-PCR and independently validated in an age- and sex-matched subset of standard-of-care treated patients of the TCGA GBM cohort (n=58). Pathway analysis suggested tumorigenesis-associated processes such as immune response, extracellular matrix organization, axon guidance, signalling by NGF, GPCR and Wnt. Here, we describe the identification and independent validation of a 4-miRNA signature that allows stratification of GBM patients into different prognostic groups in combination with one defined threshold and set of coefficients that could be utilized as diagnostic tool to identify GBM patients for improved and/or alternative treatment approaches." @default.
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• W2416509920 date "2016-06-11" @default.
• W2416509920 modified "2023-10-15" @default.
• W2416509920 title "A 4-miRNA signature predicts the therapeutic outcome of glioblastoma" @default.
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• W2416509920 doi "https://doi.org/10.18632/oncotarget.9945" @default.
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