title: Validation Study: Response-Predictive Gene Expression Profiling of Glioma Progenitor Cells In Vitro.
abstract: BACKGROUND
  In a previous publication we introduced a novel approach to identify genes that hold predictive information about treatment outcome. A linear regression model was fitted by using the least angle regression algorithm (LARS) with the expression profiles of a construction set of 18 glioma progenitor cells enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed predicting therapy-induced impairment of proliferation in vitro. Prediction performance was validated in leave one out cross validation.
  
  
  METHODS
  In this study, we used an additional validation set of 18 serum-free short-term treated in vitro cell cultures to test the predictive properties of the signature in an independent cohort. We assessed proliferation rates together with transcriptome-wide expression profiles after Sunitinib treatment of each individual cell culture, following the methods of the previous publication.
  
  
  RESULTS
  We confirmed treatment-induced expression changes in our validation set, but our signature failed to predict proliferation inhibition. Neither re-calculation of the combined dataset with all 36 BTIC cultures nor separation of samples into TCGA subclasses did generate a proliferation prediction.
  
  
  CONCLUSIONS
  Although the gene signature published from our construction set exhibited good prediction accuracy in cross validation, we were not able to validate the signature in an independent validation data set. Reasons could be regression to the mean, the moderate numbers of samples, or too low differences in the response to proliferation inhibition in the validation set. At this stage and based on the presented results, we conclude that the signature does not warrant further developmental steps towards clinical application.
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Moeckel
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Arabel
authors.initials: A
authors.lastname: Vollmann-Zwerenz
authors.affiliation: Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.affiliation: Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brawanski
authors.affiliation: Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Riemenschneider
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.affiliation: Institute of Biochemistry (Emil Fischer-Zentrum), Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.affiliation: Institute for Functional Genomics, University of Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D046228:Microarray Analysis; D014411:Neoplastic Stem Cells; D011758:Pyrroles / Q000494:pharmacology; D000077210:Sunitinib
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib