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The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH-wildtype primary glioblastoma.
Haynes, Harry R; White, Paul; Hares, Kelly M; Redondo, Juliana; Kemp, Kevin C; Singleton, William G B; Killick-Cole, Clare L; Stevens, Jonathan R; Garadi, Krishnakumar; Guglani, Sam; Wilkins, Alastair; Kurian, Kathreena M.
Afiliación
  • Haynes HR; Brain Tumour Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • White P; Applied Statistics Group, University of the West of England, Bristol, UK.
  • Hares KM; MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Redondo J; MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Kemp KC; MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Singleton WGB; Functional Neurosurgery Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Killick-Cole CL; Functional Neurosurgery Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Stevens JR; Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK.
  • Garadi K; Bristol Haematology and Oncology Centre, University Hospital Bristol Trust, Bristol, UK.
  • Guglani S; Gloucestershire Oncology Centre, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK.
  • Wilkins A; MS and Stem Cell Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
  • Kurian KM; Brain Tumour Research Group, Institute of Clinical Neurosciences, University of Bristol, Bristol, UK.
Histopathology ; 70(7): 1030-1043, 2017 Jun.
Article en En | MEDLINE | ID: mdl-27926792
AIMS: 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. METHODS AND 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Glioblastoma / PPAR alfa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Histopathology Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Glioblastoma / PPAR alfa Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Child / Female / Humans / Male / Middle aged Idioma: En Revista: Histopathology Año: 2017 Tipo del documento: Article Pais de publicación: Reino Unido