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Updated: Jun 3, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Comprehensive Transcriptomic Analysis Reveals Cell-Type-Specific Roles of Human Odorant Receptors in Glioblastoma and
Hee Jin Cho1,2, Dong Jun Yeo1,2, HeeWoong Yang3
1Department of Biomedical Convergence Science and Technology, Advanced Institute of Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea.
Abstract:
Odorant receptors (ORs), which constitute approximately 50% of all human G protein-coupled receptors, are increasingly recognized for their diverse roles beyond odor perception, including functions in various pathological conditions like brain diseases and cancers. However, the roles of ORs in glioblastoma (GBM), the most aggressive primary brain tumor with a median survival of only 15 months, remain largely unexplored. Here, we performed an integrated transcriptomic analysis combining The Cancer Genome Atlas RNA-seq and single-cell RNA sequencing data from GBM patients to uncover cell-type-specific roles of ORs within the tumor and its microenvironment. Our findings reveal that ORs display distinct expression patterns, with OR51E1 enriched in pericytes linked to vascular remodeling and angiogenesis, OR2B11 associated with tumor-associated macrophages supporting immunosuppressive phenotypes, and OR2L13 correlated with synaptic activity in recurrent tumors, potentially mediating treatment-induced neuronal adaptations. These results highlight ORs as potential therapeutic targets, offering new insights into their regulatory roles in GBM progression, immune modulation, and treatment resistance.
Insights
Odorant receptors (ORs) play key roles in glioblastoma (GBM). This study identifies specific ORs in GBM cells, macrophages, and pericytes, revealing their potential as therapeutic targets for this aggressive brain cancer.
Area of Science:
- Neuroscience
- Oncology
- Genomics
Background:
- Odorant receptors (ORs) are G protein-coupled receptors with emerging roles beyond olfaction.
- Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options.
- The function of ORs in GBM remains largely uninvestigated.
Purpose of the Study:
- To investigate the cell-type-specific roles of ORs in glioblastoma.
- To identify potential therapeutic targets within the OR family for GBM treatment.
Main Methods:
- Integrated transcriptomic analysis of GBM patient data.
- Utilized The Cancer Genome Atlas (TCGA) RNA-seq and single-cell RNA sequencing (scRNA-seq) data.
- Examined OR expression patterns in tumor cells and the microenvironment.
Main Results:
- Distinct OR expression patterns were observed across different cell types in GBM.
- OR51E1 was enriched in pericytes, linked to angiogenesis.
- OR2B11 correlated with immunosuppressive tumor-associated macrophages.
- OR2L13 was associated with synaptic activity in recurrent tumors, suggesting roles in treatment adaptation.
Conclusions:
- ORs exhibit diverse, cell-type-specific functions within the GBM microenvironment.
- Specific ORs like OR51E1, OR2B11, and OR2L13 are potential therapeutic targets for GBM.
- Understanding OR roles offers new avenues for GBM progression, immune modulation, and treatment resistance strategies.
