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

Suhas Vasaikar, Giorgos Tsipras, Natalia Landázuri, Helena Costa, Vanessa Wilhelmi, Patrick Scicluna, Huanhuan L. Cui, Abdul-Aleem Mohammad, Belghis Davoudi, Mingmei Shang, Sharan Ananthaseshan, Klas Strååt, Giuseppe Stragliotto, Afsar Rahbar, Kum Thong Wong, Jesper Tegner, Koon-Chu Yaiw, Cecilia Söderberg-Naucler

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. 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. 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. ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.