gms | German Medical Science

Objective: The epithelial-mesenchmal transition (EMT) is a strategic mechanism for numerous developmental processes includingmesodermformation andneural tubeformation. EMT-pathways exist also in organfibrosis, wound healingand in the initiation ofmetastasisas well in cancer progression. Stimulation of E- and N-cadherine supports the expression and invasion of EMT-markers. Additional EMT-components are ZEB1 and CDK1. ZEB1 as transcription factor promotes GBM invasion and chemoresistance. CDK1 is a kinase responsible for phosphorylation of important binding partners in the EMT-pathway. In this study we investigated the effect of the EMT-components ZEB1, CDK1, N-Cad and E-Cad expression in MGMT-methylated and unmethylated human glioblastomas and their prognostic value for overall survival (OS) and progression free survival (PFS).

Methods: In 44 glioblastoma patients and in one normal brain tissue ZEB1, CDK1, N-Cad and E-Cad expression were determined by performing immunohistochemistry (IHC) and quantitative real-time PCR (qPCR). Gene expression levels, between patient groups for qPCR and immunohistochemical data were compared using chi-square-test. The association between ZEB1, CDK1, N-Cad and E-Cad expression, and progression-free- and overall survival were analyzed using the Kaplan-Meier technique. P-values of <0.05 were considered statistically significant.

Results: Patients' mean age at diagnosis was 63.8±11.5 years. Median survival was 15.8± 20.2 months. The median survival time of MGMT-promotor-methylated patients was 22 months, without MGMT-promotor-methylation 9 months. On protein level, ZEB1 expression was significantly higher in glioblastoma (IRS=21.97 ± 6.8 vs. 4.7 ± 5.9; p=0.0003) than in normal brain tissue. There was a tendency to a negative correlation between ZEB1 expression and PFS (r= -0.036; p>0.05) and between ZEB1 and OS (r= -0.031; p=>0.05). On the mRNA level, CDK1 expression was higher than in the protein level (PCR= 24.1± 26.3 vs. IRS=5.8 ± 4.1). There was no correlation between the CDK1, N-Cad or E-Cad expression and PFS or OS.

Conclusion: ZEB1 gene is significantly altered in glioblastomas. High expression of ZEB1 on protein level tended to be associated with a shorter PFS and OS. The CDK 1 expression and expression of E- and N-cadherine does not play a main role in the EMT pathway in glioblastomas.