Odorant G protein-coupled receptors as potential therapeutic targets for adult diffuse gliomas: a systematic analysis and review
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Odorant receptors (ORs) account for about 60% of all humanG protein-coupled receptors (GPCRs). OR expression outsideof the nose has functions distinct from odor perception, andmay contribute to the pathogenesis of disorders including braindiseases and cancers. Glioma is the most common adult malignantbrain tumor and requires novel therapeutic strategies toimprove clinical outcomes. Here, we outlined the expressionof 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 biomarkerof unfavorable overall survival, and OR2C1 (mouse Olfr15) wasidentified as a potential biomarker of favorable overall survivalin isocitrate dehydrogenase (IDH) wild-type glioma. In additionto transcriptomic analysis, mutational profiles revealed that somaticmutations in OR genes were detected in > 60% of gliomasamples. OR5D18 (mouse Olfr1155) was the most frequentlymutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDHwild-type-specific mutation. Based on this systematic analysis andreview of the genomic and transcriptomic profiles of ORs inglioma, we suggest that ORs are potential biomarkers and therapeutictargets for glioma.
Abstract
Odorant receptors (ORs) account for about 60% of all humanG protein-coupled receptors (GPCRs). OR expression outsideof the nose has functions distinct from odor perception, andmay contribute to the pathogenesis of disorders including braindiseases and cancers. Glioma is the most common adult malignantbrain tumor and requires novel therapeutic strategies toimprove clinical outcomes. Here, we outlined the expressionof 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 biomarkerof unfavorable overall survival, and OR2C1 (mouse Olfr15) wasidentified as a potential biomarker of favorable overall survivalin isocitrate dehydrogenase (IDH) wild-type glioma. In additionto transcriptomic analysis, mutational profiles revealed that somaticmutations in OR genes were detected in > 60% of gliomasamples. OR5D18 (mouse Olfr1155) was the most frequentlymutated OR gene, and OR5AR1 (mouse Olfr1019) showed IDHwild-type-specific mutation. Based on this systematic analysis andreview of the genomic and transcriptomic profiles of ORs inglioma, we suggest that ORs are potential biomarkers and therapeutictargets for glioma.
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