Background: Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment. Methods: Data from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells. Results: By bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer. Conclusions: ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.
Bibliographical noteFunding Information:
This work was supported by Sten A Olssons Foundation for Research and Culture, Family Erling-Persson Foundation, Torsten Söderberg Foundation, BILTEMA Foundation, lngaBritt and Arne Lundbergs Foundation, Stichting af Jochnick Foundation, Jane and Dan Olssons Research Foundation, Nexttobe, Swedish Cancer Foundation, Children’s Cancer Foundation, Swedish Medical Research Council, Thematic Cardiovascular Research Center and Stockholm County Council, and the Swedish Heart-Lung Foundation, VINNOVA-BIO-X and Medivir AB (all to CSN), Cure cancer /Bota Cancer (to KCY). The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
© 2018 The Author(s).
- Endothelin B receptor
- Endothelin receptor antagonists
ASJC Scopus subject areas
- Cancer Research
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Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?
Vasaikar, S. (Creator), Tsipras, G. (Creator), Landázuri, N. (Creator), Costa, H. (Creator), Wilhelmi, V. (Creator), Scicluna, P. (Creator), Cui, H. L. (Creator), Mohammad, A. (Creator), Davoudi, B. (Creator), Shang, M. (Creator), Ananthaseshan, S. (Creator), Strååt, K. (Creator), Stragliotto, G. (Creator), Rahbar, A. (Creator), Wong, K. T. (Creator), Tegner, J. (Creator), Yaiw, K. (Creator), Söderberg-Naucler, C. (Creator), Vasaikar, S. (Creator), Tsipras, G. (Creator), Landázuri, N. (Creator), Costa, H. (Creator), Wilhelmi, V. (Creator), Scicluna, P. (Creator), Cui, H. L. (Creator), Mohammad, A. (Creator), Davoudi, B. (Creator), Shang, M. (Creator), Ananthaseshan, S. (Creator), Strååt, K. (Creator), Stragliotto, G. (Creator), Rahbar, A. (Creator), Wong, K. T. (Creator), Yaiw, K. (Creator) & Söderberg-Naucler, C. (Creator), figshare, 2018