Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

Vasaikar, Suhas and Tsipras, Giorgos and Landázuri, Natalia and Costa, Helena and Wilhelmi, Vanessa and Scicluna, Patrick and Cui, Huanhuan L. and Mohammad, Abdul Aleem and Davoudi, Belghis and Shang, Mingmei and Ananthaseshan, Sharan and Strååt, Klas and Stragliotto, Giuseppe and Rahbar, Afsar and Wong, Kum Thong and Tegner, Jesper and Yaiw, Koon Chu and Söderberg-Naucler, Cecilia (2018) Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target? BMC Cancer, 18 (1). p. 154. ISSN 1471-2407, DOI https://doi.org/10.1186/s12885-018-4012-7.

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Official URL: https://doi.org/10.1186/s12885-018-4012-7


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.

Item Type: Article
Uncontrolled Keywords: Endothelin B receptor; Endothelin receptor antagonists; Glioblastoma
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 21 Feb 2019 04:47
Last Modified: 21 Feb 2019 04:47
URI: http://eprints.um.edu.my/id/eprint/20429

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