The prostanoid pathway contains potential prognostic markers for glioblastoma

• Published in: Prostaglandins & other lipid mediators 2018-07, Vol.137, p.52-62
• Main Authors: Panagopoulos, Alexandros Theodoros, Gomes, Renata Nascimento, Almeida, Fernando Gonçalves, da Costa Souza, Felipe, Veiga, José Carlos Esteves, Nicolaou, Anna, Colquhoun, Alison
• Format: Article
• Language: English
• Subjects: 15-hydroxyprostaglandin dehydrogenase; Glioma; Prostaglandin E2; Prostaglandin reductase 1; Prostanoids
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2018.06.003

•This is the first report linking prostanoid metabolism and its degradation pathway to survival in glioma patients.•The intratumoral concentrations of PGE2 and its degradation products (PGEM’s) are related to patient survival as is the concentration of PGF2α.•Our findings highlight the potential importance of the enzymes 15HPGD and PTGR1 as prognostic biomarkers which could be used to predict survival outcome of glioblastoma patients.•Controlling the balance between the activities of these two enzymes could also be a promising target for the development of novel treatment options in the future. Prostanoids derived from the activity of cyclooxygenases and their respective synthases contribute to both active inflammation and immune response in the tumor microenvironment. Their synthesis, deactivation and role in glioma biology have not yet been fully explored and require further study. Using quantitative real time PCR, gas chromatography/ electron impact mass spectrometry and liquid chromatography/ electrospray ionization tandem mass spectrometry, we have further characterized the prostanoid pathway in grade IV glioblastoma (GBM). We observed significant correlations between high mRNA expression levels and poor patient survival for microsomal PGE synthase 1 (mPGES1) and prostaglandin reductase 1 (PTGR1). Conversely, high mRNA expression levels for 15-hydroxyprostaglandin dehydrogenase (15-HPGD) were correlated with better patient survival. GBMs had a higher quantity of the prostanoid precursor, arachidonic acid, versus grade II/III tumors and in GBMs a significant positive correlation was found between arachidonic acid and PGE2 content. GBMs also had higher concentrations of TXB2, PGD2, PGE2 and PGF2α versus grade II/III tumors. A significant decrease in survival was detected for high versus low PGE2, PGE2 + PGE2 deactivation products (PGEMs) and PGF2α in GBM patients. Our data show the potential importance of prostanoid metabolism in the progression towards GBM and provide evidence that higher PGE2 and PGF2α concentrations in the tumor are correlated with poorer patient survival. Our findings highlight the potential importance of the enzymes 15-HPGD and PTGR1 as prognostic biomarkers which could be used to predict survival outcome of patients with GBM.