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

Vasaikar S 1 , Tsipras G 1 , Landázuri N 1 , Costa H 2 , Wilhelmi V 2 , Scicluna P 2 Show all authors , Cui HL 2 , Mohammad AA 2 , Davoudi B 2 , Shang M 1 , Ananthaseshan S 2 , Strååt K 3 , Stragliotto G 4 , Rahbar A 2 , Wong KT 5 , Tegner J 1 , Yaiw KC 6 , Söderberg-Naucler C 7

Affiliations 

  • 1 Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  • 2 Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden
  • 3 Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
  • 4 Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
  • 5 Department of Pathology, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. ykcywx@yahoo.com
  • 7 Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden. Cecilia.Naucler@ki.se
BMC Cancer, 2018 02 06;18(1):154.
PMID: 29409474 DOI: 10.1186/s12885-018-4012-7

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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