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Overexpression of oncostatin M receptor regulates local immune response in glioblastoma
Qing Guo1, Ge-Fei Guan1, Jing-Yuan Cao1
1Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Abstract:
Glioblastoma (GBM) is the most lethal cancer in central nervous system. It is urgently needed to look for novel therapeutics for GBM. Oncostatin M receptor (OSMR) is a cytokine receptor gene of IL-6 family and has been reported to be involved in regulating GBM tumorigenesis. However, the role of OSMR regulating the disrupted immune response in GBM need to be further investigated. Three gene expression profiles, Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) data set (GSE16011), were enrolled in our study and used for OSMR expression and survival analysis. The expression of OSMR was further verified with immunohistochemistry and western blot analysis in glioma tissues. Microenvironment cell populations-counter (MCP-counter) was applied for analyzing the relationship between OSMR expression and nontumor cells. The functions of OSMR in GBM was investigated by Gene Ontology, Gene set enrichment analysis (GSEA), gene set variation analysis and so on. The analysis of cytokine receptor activity-related genes in glioma identifies OSMR as a gene with an independent predictive factor for progressive malignancy in GBM. Furthermore, OSMR expression is a prognostic marker in the response prediction to radiotherapy and chemotherapy. OSMR contributes to the regulation of local immune response and extracellular matrix process in GBM. Our findings define an important role of OSMR in the regulation of local immune response in GBM, which may suggest OSMR as a possible biomarker in developing new therapeutic immune strategies in GBM.
Insights
Oncostatin M receptor (OSMR) plays a key role in glioblastoma (GBM) immune response and extracellular matrix regulation. OSMR is a potential biomarker for predicting treatment response and developing new immune therapies for GBM.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Glioblastoma (GBM) is a highly lethal central nervous system cancer requiring novel therapeutics.
- Oncostatin M receptor (OSMR), an IL-6 family cytokine receptor, is implicated in GBM tumorigenesis.
- The specific role of OSMR in regulating GBM's immune microenvironment remains under-investigated.
Purpose of the Study:
- To investigate the role of OSMR in glioblastoma.
- To analyze OSMR expression and its correlation with patient survival and treatment response.
- To explore OSMR's function in the GBM immune microenvironment and extracellular matrix.
Main Methods:
- Utilized gene expression datasets (CGGA, TCGA, GEO) for OSMR expression and survival analysis.
- Validated OSMR expression using immunohistochemistry and western blot in glioma tissues.
- Applied MCP-counter, Gene Ontology, GSEA, and GSVA to analyze OSMR's association with immune cells and its functional roles.
Main Results:
- OSMR was identified as a gene associated with cytokine receptor activity and an independent predictor of GBM malignancy.
- OSMR expression serves as a prognostic marker for radiotherapy and chemotherapy response.
- OSMR influences local immune responses and extracellular matrix processes in GBM.
Conclusions:
- OSMR is crucial in regulating the local immune response within the GBM microenvironment.
- OSMR may serve as a valuable biomarker for predicting treatment outcomes.
- Targeting OSMR could lead to novel therapeutic immune strategies for glioblastoma.
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