title: Transcriptomic profiling of Forkhead box transcription factors in adult glioblastoma multiforme.
abstract: BACKGROUND
  The Forkhead box transcription factor (FOX) family plays an essential role in embryogenesis, especially during brain development. Our hypothesis is that de-regulation of FOX genes may contribute to aggressive tumor biology and therapy resistance in patients with glioblastoma multiforme (GBM).
  
  
  METHODS
  Univariate and multivariate analyses were performed to evaluate prognostic significance of transcript levels of 31 FOX genes in a test set of GBM patients (n=191) and validated them in The Cancer Genome Atlas (TCGA) cohort comprising of 508 adult cases of GBM. The predictive significance of key FOX genes was investigated in patients who received chemotherapy or radiotherapy.
  
  
  RESULTS
  Low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high FOXG1 mRNA were associated with poor survival in the test and TCGA validation cohorts. In multivariate analysis, low FOXA2 mRNA, low FOXN2 mRNA, low FOXN3 mRNA and high FOXG1 mRNA remained independently associated with poor survival in the test and TCGA validation cohorts. In patients who received chemotherapy or radiotherapy, low FOXA2 mRNA, low FOXN2 mRNA and high FOXG1 mRNA correlated with adverse outcomes in the TCGA validation cohort.
  
  
  CONCLUSIONS
  To our knowledge, our data provide the first comprehensive clinical evidence that FOXA2, FOXN2, FOXN3 and FOXG1 are promising biomarkers of GBM and warrant further investigation.
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K.
authors.forename: Emily
authors.initials: E
authors.lastname: Robertson
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K. Department of Oncology, Nottingham University Hospitals, Nottingham, U.K.
authors.forename: Christina
authors.initials: C
authors.lastname: Perry
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K.
authors.forename: Rachel
authors.initials: R
authors.lastname: Doherty
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham University Hospitals, Nottingham, U.K. Department of Oncology, Nottingham University Hospitals, Nottingham, U.K.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066264:Datasets as Topic; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D059467:Transcriptome; D055815:Young Adult
chemical_list: D051858:Forkhead Transcription Factors
keywords: FOX transcription factors; Glioblastoma multiforme; predictive factor; prognostic factor