Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Cell and Molecular Immunology, Experimental Cardiovascular Unit, Departments of Medicine and Neurology, Center for Molecular Medicine, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
BMC Cancer. 2018 Feb 6;18(1):154. doi: 10.1186/s12885-018-4012-7.
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.
胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤，中位生存时间为 12-15 个月。由于临床结果不确定，除了现有的标志物之外，还需要额外的预后标志物。由于内皮素 B 受体（ETBR）在神经胶质瘤中过度表达，我们旨在测试 ETBR 是否是 GBM 的有用预后标志物，并研究临床上可用的内皮素受体拮抗剂（ERA）是否可用于该疾病的治疗。
分析来自癌症基因组图谱和基因表达综合数据库的数据，以评估 ETBR 的表达。为了进行生存分析，对 25 名瑞典患者的胶质母细胞瘤样本进行了 ETBR 免疫染色，并将结果与临床病史相关联。通过蛋白质-蛋白质相互作用网络分析评估了 ETBR 的可成药性。用体外测定法分析了 ERA 在 GBM 和乳腺癌细胞中的毒性。
通过生物信息学分析，发现 ETBR 在胶质母细胞瘤患者中上调，其表达水平与生存时间缩短相关。ETBR 与参与癌症发病机制的关键蛋白相互作用，表明它是一个可成药的靶点。体外生存力测定表明，ERA 可能有希望用于治疗胶质母细胞瘤和乳腺癌。
ETBR 在胶质母细胞瘤和其他癌症中过度表达，可能是胶质母细胞瘤的预后标志物。ERA 可能对治疗癌症患者有用。
