TY  - JOUR
A1  - Niyazi, Karim-Maximilian
A1  - Pitea, Adriana
A1  - Mittelbronn, Michel Guy André
A1  - Steinbach, Joachim Peter
A1  - Sticht, Carsten
A1  - Zehentmayr, Franz
A1  - Piehlmaier, Daniel
A1  - Zitzelsberger, Horst
A1  - Ganswindt, Ute
A1  - Rödel, Claus
A1  - Lauber, Kirsten
A1  - Belka, Claus
A1  - Unger, Kristian
T1  - A 4-miRNA signature predicts the therapeutic outcome of glioblastoma
T2  - Oncotarget
N2  - 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.
KW  - glioblastoma
KW  - miRNA
KW  - signature
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/42234
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-422340
SN  - 1949-2553
N1  - Licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 29
SP  - 45764
EP  - 45775
PB  - Impact Journals LLC
CY  - [S.l.]
ER  -