气味性 G 蛋白偶联受体作为成人弥漫性神经胶质瘤潜在治疗靶点的系统分析与综述。
Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review.
机构信息
Department of Biomedical Convergence Science and Technology, Kyungpook National University, Daegu 41566; Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea.
Department of New Biology, DGIST, Daegu 42988; New Biology Research Center (NBRC), DGIST, Daegu 42988; Korea Brain Research Institute (KBRI), Daegu 41062, Korea.
出版信息
BMB Rep. 2021 Dec;54(12):601-607. doi: 10.5483/BMBRep.2021.54.12.165.
Odorant receptors (ORs) account for about 60% of all human G protein-coupled receptors (GPCRs). OR expression outside of the nose has functions distinct from odor perception, and may contribute to the pathogenesis of disorders including brain diseases and cancers. Glioma is the most common adult malignant brain tumor and requires novel therapeutic strategies to improve clinical outcomes. Here, we outlined the expression of brain ORs and investigated OR expression levels in glioma. Although most ORs were not ubiquitously expressed in gliomas, a subset of ORs displayed glioma subtype-specific expression. Moreover, through systematic survival analysis on OR genes, OR51E1 (mouse Olfr558) was identified as a potential biomarker of unfavorable overall survival, and OR2C1 (mouse Olfr15) was identified as a potential biomarker of favorable overall survival in isocitrate dehydrogenase (IDH) wild-type glioma. In addition to transcriptomic analysis, mutational profiles revealed that somatic mutations in OR genes were detected in ＞ 60% of glioma samples. OR5D18 (mouse Olfr1155) was the most frequently mutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDH wild-type-specific mutation. Based on this systematic analysis and review of the genomic and transcriptomic profiles of ORs in glioma, we suggest that ORs are potential biomarkers and therapeutic targets for glioma. [BMB Reports 2021; 54(12): 601-607].
气味受体 (ORs) 约占人类 G 蛋白偶联受体 (GPCRs) 的 60%。OR 在鼻子以外的表达具有不同于嗅觉感知的功能，并且可能有助于包括脑部疾病和癌症在内的多种疾病的发病机制。神经胶质瘤是最常见的成人恶性脑肿瘤，需要新的治疗策略来改善临床结果。在这里，我们概述了大脑 OR 的表达，并研究了神经胶质瘤中的 OR 表达水平。尽管大多数 OR 并非在神经胶质瘤中普遍表达，但一部分 OR 表现出神经胶质瘤亚型特异性表达。此外，通过对 OR 基因进行系统的生存分析，发现 OR51E1（小鼠 Olfr558）可作为总生存期不良的潜在生物标志物，OR2C1（小鼠 Olfr15）可作为 IDH 野生型神经胶质瘤总生存期良好的潜在生物标志物。除了转录组分析外，突变谱显示 OR 基因的体细胞突变在＞60%的神经胶质瘤样本中被检测到。OR5D18（小鼠 Olfr1155）是最常突变的 OR 基因，而 OR5AR1（小鼠 Olfr1019）则表现出 IDH 野生型特异性突变。基于对 OR 在神经胶质瘤中的基因组和转录组特征的系统分析和综述，我们认为 OR 是神经胶质瘤的潜在生物标志物和治疗靶点。[BMB 报告 2021；54(12)：601-607]。
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