title: Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jiri
authors.initials: J
authors.lastname: Sana
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Lakomy
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Department of Pathology, University Hospital Brno, Brno 62500, Czech Republic.
authors.forename: Leos
authors.initials: L
authors.lastname: Kren
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Department of Neurosurgery, University Hospital Brno, Brno 62500, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Fadrus
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Department of Neurosurgery, University Hospital Brno, Brno 62500, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Smrcka
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Andrej
authors.initials: A
authors.lastname: Besse
authors.affiliation: Institute of Clinical Biochemistry and Diagnostics, Faculty of Medicine and Faculty Hospital in Hradec Kralove, Charles University, Hradec Kralove 50005, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Nekvindova
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, First Department of Pathological Anatomy, St. Anne's University Hospital, Brno 65691, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Hermanova
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Department of Neurosurgery, St. Anne's University Hospital, Brno 65691, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Jancalek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc 77900, Czech Republic and.
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.affiliation: Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic, Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Slampa
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic, Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic.
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.affiliation: 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, on.slaby@gmail.com.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012189:Retrospective Studies; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes