title: The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH-wildtype primary glioblastoma.
abstract: OBJECTIVE
  PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients' clinicopathological features and other molecular markers associated with gliomagenesis.
  
  
  RESULTS
  With protein immunoblotting techniques and reverse transcription quantitative real-time PCR, PPARα was found to be significantly overexpressed in glioblastoma compared with control brain tissue (P = 0.032 and P = 0.005). PPARA gene expression was found to be enriched in the classical glioblastoma subtype within The Cancer Genome Atlas (TCGA) dataset. Although not associated with overall survival when assessed by immunohistochemistry, cross-validation with the TCGA dataset and multivariate analyses identified PPARA gene expression as an independent prognostic marker for overall survival (P = 0.042). Finally, hierarchical clustering revealed novel, significant associations between high PPARA expression and a putative set of glioblastoma molecular mediators including EMX2, AQP4, and NTRK2.
  
  
  CONCLUSIONS
  PPARα is overexpressed in primary glioblastoma and high PPARA expression functions as an independent prognostic marker in the glioblastoma TCGA dataset. Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists.
authors.affiliation: Brain Tumour Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Harry R
authors.initials: HR
authors.lastname: Haynes
authors.affiliation: Applied Statistics Group, University of the West of England, Bristol, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: White
authors.affiliation: MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Hares
authors.affiliation: MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Juliana
authors.initials: J
authors.lastname: Redondo
authors.affiliation: MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kemp
authors.affiliation: Functional Neurosurgery Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: William G B
authors.initials: WGB
authors.lastname: Singleton
authors.affiliation: Functional Neurosurgery Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Killick-Cole
authors.affiliation: Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Stevens
authors.affiliation: Bristol Haematology and Oncology Centre, University Hospital Bristol Trust, Bristol, UK.
authors.forename: Krishnakumar
authors.initials: K
authors.lastname: Garadi
authors.affiliation: Gloucestershire Oncology Centre, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Guglani
authors.affiliation: MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Wilkins
authors.affiliation: Brain Tumour Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
authors.forename: Kathreena M
authors.initials: KM
authors.lastname: Kurian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002648:Child; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D047493:PPAR alpha; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: PPARalpha; biomarker; glioblastoma