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The transcription factor PPARα is overexpressed and is associated with a favourable prognosis in IDH ‐wildtype primary glioblastoma
Author(s) -
Haynes Harry R,
White Paul,
Hares Kelly M,
Redondo Juliana,
Kemp Kevin C,
Singleton William G B,
KillickCole Clare L,
Stevens Jonathan R,
Garadi Krishnakumar,
Guglani Sam,
Wilkins Alastair,
Kurian Kathreena M
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13142
Subject(s) - biology , transcription factor , peroxisome proliferator activated receptor , glioblastoma , immunohistochemistry , cancer research , gene expression , medicine , oncology , gene , genetics , immunology
Aims PPAR α agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPAR α in large‐scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPAR α in primary glioblastoma, the relationship between PPAR α 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 , PPAR α 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 PPAR α expression in glioblastoma models in response to PPAR α agonists.