title: A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab.
abstract: We investigated whether microRNA expression data from glioblastoma could be used to produce a profile that defines a bevacizumab responsive group of patients.
  
  
  
  TCGA microRNA expression data from tumors resected at first diagnosis of glioblastoma in patients treated with bevacizumab at any time during the course of their disease were randomly separated into training (n = 50) and test (n = 37) groups for model generation. MicroRNA-seq data for 51 patients whose treatment included bevacizumab in the BELOB trial were used as an independent validation cohort.
  
  
  
  Using penalized regression we identified 8 microRNAs as potential predictors of overall survival in the training set. We dichotomized the response score based on the most prognostic minimum of a density plot of the response scores (log-rank HR = 0.16, p = 1.2e(-5)) and validated the profile in the test cohort (one-sided log-rank HR = 0.34, p = 0.026). Analysis of the profile using all samples in the TCGA glioblastoma dataset, regardless of treatment received, (n = 473) showed that the prediction of patient benefit was not significant (HR = 0.84, p = 0.083) suggesting the profile is specific to bevacizumab. Further independent validation of our microRNA profile in RNA-seq data from patients treated with bevacizumab (alone or in combination with CCNU) at glioblastoma recurrence in the BELOB trial confirmed that our microRNA profile predicted patient benefit from bevacizumab (HR = 0.59, p = 0.043).
  
  
  
  We have identified and validated an 8-microRNA profile that predicts overall survival in patients with glioblastoma treated with bevacizumab. This may be useful for identifying patients who are likely to benefit from this agent.
authors.affiliation: Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds LS9 7TF, UK. Electronic address: Josielouise.hayes@ucsf.edu.
authors.forename: Josie
authors.initials: J
authors.lastname: Hayes
authors.affiliation: Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Helene
authors.initials: H
authors.lastname: Thygesen
authors.affiliation: Clinical Trials Research Unit (CTRU), University of Leeds, 71-75 Clarendon Road, Leeds, West Yorkshire LS2 9JT, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Gregory
authors.affiliation: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences and Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Westhead
authors.affiliation: Department of Neurology, Brain Tumor Center, Erasmus MC Cancer Institute, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: Pim J
authors.initials: PJ
authors.lastname: French
authors.affiliation: Department of Neurology, Brain Tumor Center, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Van Den Bent
authors.affiliation: Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Lawler
authors.affiliation: Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds LS9 7TF, UK.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Short
mesh_terms: D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; D000068258:Bevacizumab
keywords: Bevacizumab; Glioblastoma; Glioma; Prediction; microRNA