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Published on: January 9, 2019
Identification of three tumor antigens and immune subtypes for mRNA vaccine development in diffuse glioma
Quanwei Zhou1, Xuejun Yan2, Hecheng Zhu3
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
Abstract:
Rationale: Diffuse glioma patients have high mortality and recurrence despite multimodal therapies. This study aims to identify the potential tumor antigens for mRNA vaccines and subtypes suitable for the immunotherapy of patients with diffuse glioma. Methods: Gene expression profiles and corresponding clinical information were obtained from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) databases. Genetic alterations were extracted from cBioPortal. Differential gene analysis, survival analysis, correlation analysis, consensus clustering analysis, and immune cell infiltration analysis were conducted based on the various databases. Finally, the hub genes, the modules related to tumor antigens, and the immune subtypes were identified using WGCNA method. Results: Three over-expressed, amplified, and mutated tumor antigens, including KDR, COL1A2, and SAMD9, were associated with clinical outcomes. The expression of the three genes had a positive correlation with the abundance of antigen-presenting cells (APCs) and APC marker expression. Subsequently, three immune subtypes (Ims1, Ims2, and Ims3) were distinguished in the TCGA cohort, which exhibited distinct molecular, cellular, and clinical characteristics consistent with the CGGA cohort. Diffuse gliomas with subtype Ims1 were more malignant with immunosuppressive phenotypes and more associated with poor prognosis than the other two subtypes. The three antigens and the immune checkpoints were differentially expressed among the three immune subtypes. Finally, functional enrichment analysis of the genes related to tumor antigens and immune subtypes suggested that they are enriched in many immune-associated processes. Conclusions: KDR, COL1A2, and SAMD9 are potential antigens for developing mRNA vaccines against diffuse glioma. The results suggest that immunotherapy targeting these three antigens is more suitable for patients with subtype Ims1. This study provides insights into immunotherapy for diffuse glioma.
Insights
This study identifies KDR, COL1A2, and SAMD9 as potential tumor antigens for diffuse glioma mRNA vaccines. Immunotherapy targeting these antigens may benefit patients with the identified Ims1 subtype, offering new insights for diffuse glioma treatment.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Diffuse gliomas present significant mortality and recurrence challenges despite current treatments.
- Identifying novel therapeutic targets, such as tumor antigens and patient subtypes, is crucial for improving diffuse glioma outcomes.
Purpose of the Study:
- To identify potential tumor antigens for mRNA vaccine development in diffuse glioma.
- To define distinct diffuse glioma subtypes amenable to specific immunotherapies.
Main Methods:
- Utilized gene expression and clinical data from CGGA and TCGA databases.
- Performed differential gene expression, survival, correlation, and consensus clustering analyses.
- Employed Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes, tumor antigen modules, and immune subtypes.
Main Results:
- Identified KDR, COL1A2, and SAMD9 as over-expressed, amplified, and mutated tumor antigens linked to clinical outcomes.
- Discovered three distinct immune subtypes (Ims1, Ims2, Ims3) with varying molecular, cellular, and clinical characteristics.
- Found that subtype Ims1 exhibits more malignant and immunosuppressive phenotypes, correlating with poorer prognosis.
Conclusions:
- KDR, COL1A2, and SAMD9 are promising targets for diffuse glioma mRNA vaccines.
- Immunotherapy focusing on these antigens appears most suitable for diffuse glioma patients classified under subtype Ims1.
- This research offers valuable insights for advancing immunotherapy strategies in diffuse glioma.
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