A 4-miRNA signature predicts the therapeutic outcome of glioblastoma

Maximilian Niyazi, Adriana Pitea, Michel Mittelbronn, Joachim Steinbach, Carsten Sticht, Franz Zehentmayr, Daniel Piehlmaier, Horst Zitzelsberger, Ute Ganswindt, Claus Rödel, Kirsten Lauber, Claus Belka, Kristian Unger*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45764-45775
Number of pages12
JournalOncotarget
Volume7
Issue number29
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Glioblastoma
  • MiRNA
  • Signature

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