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Niyazi, M. ; Pitea, A. ; Mittelbronn, M.* ; Steinbach, J.* ; Sticht, C.* ; Zehentmayr, F.* ; Piehlmaier, D. ; Zitzelsberger, H. ; Ganswindt, U. ; Rödel, C.* ; Lauber, K. ; Belka, C. ; Unger, K.

A 4-miRNA signature predicts the therapeutic outcome of glioblastoma.

Oncotarget 7, 45764-45775 (2016)
Verlagsversion Forschungsdaten DOI PMC
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glioblastoma ; Mirna ; Signature; Newly-diagnosed Glioblastoma; Intratumoral Homogeneity; Adjuvant Temozolomide; Cell-differentiation; Microrna Expression; Glioma Patients; Bevacizumab; Survival; Rna; Radiotherapy
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 7, Heft: 29, Seiten: 45764-45775 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Verlagsort Albany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CCG Personalized Radiotherapy in Head and Neck Cancer (KKG-KRT)
Research Unit Radiation Cytogenetics (ZYTO)