Die kombinierte Überexpression von EP2 und EP4 in Glioblastomen ist mit einem kürzeren Gesamtüberleben assoziiert

Targeted therapy and personalized medicine are one of the central interests in neurooncology research. Nevertheless, therapy for glioblastoma still mainly relies on surgery followed by chemoirradiation and the search of new markers with prognostic or predictive value and in the best case targetable molecules. The prostaglandin receptors EP2 and EP4 are involved in pro tumorigenic signaling in various cancer types and there are studies suggesting a proliferative effect in glioblastoma cells. Therefore, we determined the expression of EP2 and EP4 in glioblastoma and investigated, whether their expression is associated with worse prognosis.

EP2 and EP4 expression was determined via quantitative Real-Time PCR (qPCR) and semiquantitative immunohistochemistry (IHC) in 42 glioblastoma patients, who had undergone surgery in our department between 2013 and 2020. Data on MGMT-promotor status and TERT mutation status as well as progression free survival (PFS) and overall survival (OS) were collected from patient records. Patient with ΔCT-values for EP2 or EP4 in qPCR below the median were defined as high expression group (HEG) and above the median as low expression group (LEG). For IHC expression values above the median were defined as HEG and below the median as LEG. Group comparison was done via Log-rank test and survival analyses were performed with the Kaplan-Meier method; correlation was calculated as Pearson Index in SPSS.

On mRNA level mean EP2 expression was 9.25 ± 2.56 and mean EP4 expression was 7.62 ± 2.37. In IHC mean EP2 expression value was 7.00 ± 4.12 and mean EP4 expression was 9.14 ± 5.09. No correlation with MGMT promotor status or TERT mutation was observed. Median OS and PFS showed no statistically significant difference in LEG and HEG of the single receptors, although we observed a trend towards an association of high EP4 expression in IHC with shorter OS (r = -0.278; p = 0.075) and PFS (r = -0.196; p = 0.213).Combined expression of EP2 and EP4 correlated significantly with shorter OS (r = -0.313; p=0.044) and there was a non-significant trend toward a shorter PFS (r= -0.243; p=0.121).

Combined expression of the prostaglandin receptors EP2 and EP4 is moderately associated with shorter OS in glioblastoma patients. The expression of EP4 seems to have a higher prognostic impact than expression of EP2. The detailed role of the receptors and the possibility of a therapeutic use should be further investigated.