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Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients

J. Sana, L. Radova, R. Lakomy, L. Kren, P. Fadrus, M. Smrcka, A. Besse, J. Nekvindova, M. Hermanova, R. Jancalek, M. Svoboda, M. Hajduch, P. Slampa, R. Vyzula, O. Slaby,

. 2014 ; 35 (12) : 2756-2762.

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc15014022

Grantová podpora
NT13514 MZ0 CEP - Centrální evidence projektů
NT13581 MZ0 CEP - Centrální evidence projektů

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.

Central European Institute of Technology Masaryk University Brno 62500 Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno 65653 Czech Republic Faculty of Medicine Masaryk University Brno 62500 Czech Republic

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno 65653 Czech Republic Faculty of Medicine Masaryk University Brno 62500 Czech Republic Central European Institute of Technology Masaryk University Brno 62500 Czech Republic

Faculty of Medicine Masaryk University Brno 62500 Czech Republic 1st Department of Pathological Anatomy St Anne's University Hospital Brno 65691 Czech Republic

Faculty of Medicine Masaryk University Brno 62500 Czech Republic Department of Neurosurgery St Anne's University Hospital Brno 65691 Czech Republic

Faculty of Medicine Masaryk University Brno 62500 Czech Republic Department of Neurosurgery University Hospital Brno Brno 62500 Czech Republic

Faculty of Medicine Masaryk University Brno 62500 Czech Republic Department of Pathology University Hospital Brno Brno 62500 Czech Republic

Faculty of Medicine Masaryk University Brno 62500 Czech Republic Department of Radiation Oncology Masaryk Memorial Cancer Institute Brno 65653 Czech Republic

Institute of Clinical Biochemistry and Diagnostics Faculty of Medicine and Faculty Hospital in Hradec Kralove Charles University Hradec Kralove 50005 Czech Republic

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University Olomouc Olomouc 77900 Czech Republic and

Citace poskytuje Crossref.org

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$a Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.
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