Artikel
The crucial role of SNAIL 1 and 2 in the EMT-pathway of glioblastoma patients
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Autoren
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Frank Schwarm
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Samuel Thomas
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Frederike Hagedorn
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Christian Koch
- Justus-Liebig-Universität Gießen, Klinik für Anästhesiologie und Intensivmedizin, Gießen, Deutschland
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Marco Stein
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Eberhard Uhl
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
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Malgorzata Kolodziej
- Justus-Liebig-Universität Gießen, Klinik für Neurochirurgie, Gießen, Deutschland
| Veröffentlicht: | 18. Juni 2018 |
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Gliederung
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Objective: The epithelial-mesenchymal transition (EMT)-pathway is a strategic mechanism in embryonic development and also in tissue repair. Beside this the EMT-pathway is also important in cancer. Uncontrolled activation of EMT in adult life leads to cancer growth and metastasis. SNAIL1 promotes proliferation, migration and invasion of GBM cells. The SNAIL 2 function is similar to SNAIL 1, but in addition promotes angiogenesis and tumour growth of glioblastoma (GBM) cells. Vimentin promotes EMT-like processes in GBM cell lines. In this study we investigated the effect of EMT-components SNAIL1, SNAIL 2, N-Cad, E-Cad and Vimentin expression in methylated and unmethylated human glioblastomas and its prognostic value.
Methods: In tumor specimen of 44 glioblastoma patients SNAIL1, SNAIL2, VIM, N-Cad, E-Cad expression was determined by performing quantitative real-time PCR (qPCR) and immunohistochemistry (IHC). Gene expression levels in MGMT methylated vs. unmethylated patients, gene expression levels between patient groups, both for qPCR and immunohistochemical data were compared using the Student t-test. The relationship between SNAIL1, SNAIL2 expression, and progression-free survival (PFS), and overall survival (OS) was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered to be statistically significant.
Results: Patients' mean age at diagnosis was 63.8±11.5 years. Median survival was 15.8±20.2 months. Analysis for SNAIL1 and SNAIL2 in methylated patients showed that high SNAIL1 and SNAIL2 levels are associated with a shorter median PFS compared to patients with low SNAIL1 and 2 expression (7.4 versus 1.5 months; p=0.37 and 9.3 vs. 5.1 months; p=0.50). Median OS in patients with SNAIL1 and SNAIL 2 overexpression was also reduced (17.8 vs. 11.8 months; p=0.66 and 25.0 vs. 12.3 months; p=0.42) compared to months in SNAIL 1 and 2 low expression. Unmethylated patients with SNAIL 1 and 2 overexpression showed similar tendencies to the methylated group.
Conclusion: SNAIL1 and 2 play an important role in EMT-pathway of glioblastoma. The expression of these genes shows the tendency to influence the survival time of patients. The directly inhibition of SNAIL1 and 2 could play an important part in the future therapy of glioblastoma.
