Abstract 1496: MicroRNA signature associated with poor outcome of glioblastoma patients
Authors: Jiri Sana, Radek Lakomy, Pavel Fadrus, Martin Smrcka, Pavel Slampa, Leos Kren, Marketa Hermanova, Marek Svoboda, Ondrej Slaby
Journal: Cancer Research (2014)

Abstract Background: Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor with very poor prognosis, varying therapeutic response. Therefore, it is very important to find new biomarkers which can predict a clinical outcomes and help in treatment decisions. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play key role in pathogenesis of wide range of cancer, including GBM. Aim of our study is to identify miRNA signature associated with the more aggressive phenotype of GBMs, which will enable sensitive prediction of clinical outcome in GBM patients under standard therapeutic protocols. Methods: We determined the expression profile of 667 miRNAs in tumor tissues of 58 patients with primary GBM with completed concomitant chemoradiotherapy with temozolomide according to standard Stupp protocol and 12 non-malignant brain tissues obtained from patients with drug-resistant anteromedial temporal lobe epilepsy. Methylation status of MGMT promoter (methylation-specific HRM), isocitrate dehydrogenase (IDH1) status (immunohistochemistry) and co-deletion of 1p/19q (FISH) was also evaluated. Results: We have confirmed frequencies of commonly used prognostic biomarkers in GBM patients (MGMT, IDH1, 1p/19q deletion), and observed significant correlation of MGMT methylation status, response to chemoradiotherapy with temozolomide and survival of GBM patients. We have identified specific signature of miRNAs diferentially expressed between GBM tissue and non-tumoral brain tissue from epilepsy surgeries (28 miRNAs, p&amp;lt;10-10). We have confirmed some previous observations (e.g. up-regulation of miR-21, miR-155, down-regulation of miR-128a, miR-23a) and also identified miRNAs deregulated in GBM tissue which were observed for the first time (e.g. miR-220, miR-328, miR-888, miR-504). More importantly we have found miRNA signature (miR-224, miR-31, miR-454, miR-672, miR-885-5p, miR-432) significantly associated short progression-free survival (p&amp;lt;10-6) and overall survival (p&amp;lt;10-6). Conclusions: These findings indicate that miRNAs play an important role in GBM pathogenesis and may serve not only as promising predictors of therapeutic outcome but also as potential therapeutic targets in GBM patients. This work was supported by Grant NT13549-4/2012, NT13860 4/2012, NT11214-4/2010 and NT13514-4/2012 of the Czech Ministry of Health, MH CZ - DRO (MMCI, 00209805). Citation Format: Jiri Sana, Radek Lakomy, Pavel Fadrus, Martin Smrcka, Pavel Slampa, Leos Kren, Marketa Hermanova, Marek Svoboda, Ondrej Slaby. MicroRNA signature associated with poor outcome of glioblastoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1496. doi:10.1158/1538-7445.AM2014-1496