Artikel
The prognostic value of Fas and FasL in WHO grade II glioma progression
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Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Objective: The cell-surface of tumor cells is a target for antibody-driven immunotherapy and cell-surface molecules that can be used as biomarker. The well known cell surface receptor Fas (Apo-1, CD95) plays an important role in the mechanisms of induced cell death. Targeting Fas with an antibody or its ligand FasL (CD95L, CD178) drives the cell into apoptosis. The aim of this study was to evaluate the value of Fas/FasL in WHO grade II glioma progression. As low-grade gliomas do evolve and proceed towards glioblastomas, the question was whether there is a possible use for Fas/FasL as biomarkers regarding the malignant progression and progression free survival (PFS).
Methods: All samples were classified based on the 2007 WHO classification of CNS tumors. Quantitative real-time PCR was performed with Cycler Rotor Gene Q and the Rotor-Gene SYBR Green PCR Kit (Qiagen). SDHA was used as a housekeeping gene. Data analysis was performed with Graphpad Prism 7. Statistical tests used: Log-rank test for Kaplan Meier analysis. The significance level (α) was set on 0.05. Expression levels are displayed in mean values and standard error of the mean (SEM). Tumor samples were frozen, cut, mounted on slides and fixed with paraformaldehyde and acetone. The ImmPACT DAB substrate Kit (SK-4105) was used for staining with Diaminobenzidine (DAB). Vitro-Clud was used as embedding medium for covering the coverslips.
Results: 44 patients with primary grade II gliomas (22 astrocytomas, 16 oligoastrocytomas and 6 oligodendrogliomas) were included. The patients were divided in two groups according to whether the Fas or the FasL value was higher or lower as the mean value of all patients. The two groups were compared regarding their PFS, which was set as the time in months between first resection and tumor-recurrence operation. Patients with a high FasL expression level had a significantly longer time to progression (median PFS: FasL-high 42.93 vs. FasL-low 29.93; Log-rank p<0.05). The level of Fas did not show significant difference in the median PFS (Fas-high 44.07 vs. Fas-low 35.89).
Conclusion: Fas-L may be of value as a low-grade biomarker regarding progression free survival. In order to set clear cut-off values further studies are warranted.