Abstract
BackgroundAlthough mRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. There is growing evidence that immunophenotyping can reflect the comprehensive immune status and microenvironment of the tumor, which correlates closely with treatment response and vaccination potency. The purpose of this research was to screen for effective antigens in glioma that could be used for developing mRNA vaccines and to further differentiate the immune subtypes of glioma to create an selection criteria for suitable patients for vaccination.MethodsGene expression profiles and clinical data of 698 glioma samples were extracted from The Cancer Genome Atlas, and RNA_seq data of 1018 glioma samples was gathered from Chinese Glioma Genome Atlas. Gene Expression Profiling Interactive Analysis was used to determine differential expression genes and prognostic markers, cBioPortal software was used to verify gene alterations, and Tumor Immune Estimation Resource was used to investigate the relationships among genes and immune infiltrating cells. Consistency clustering was applied for consistent matrix construction and data aggregation, Gene oncology enrichment was performed for functional annotation, and a graph learning-based dimensionality reduction method was applied to describe the subtypes of immunity.ResultsFour overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in glioma, including TP53, IDH1, C3, and TCF12. Besides, four immune subtypes of glioma (IS1-IS4) and 10 immune gene modules were identified consistently in the TCGA data. The immune subtypes had diverse molecular, cellular, and clinical features. IS1 and IS4 displayed an immune-activating phenotype and were associated with worse survival than the other two subtypes, while IS2 and IS3 had lower levels of tumor immune infiltration. Immunogenic cell death regulators and immune checkpoints were also diversely expressed in the four immune subtypes.ConclusionTP53, IDH1, C3, and TCF12 are effective antigens for the development of anti-glioma mRNA vaccines. We found four stable and repeatable immune subtypes of human glioma, the classification of the immune subtypes of glioma may play a crucial role in the predicting mRNA vaccine outcome.
Highlights
Glioma is a fatal malignancy with a 5-year survivability rate of only 5%
Five genes were strongly correlated with Overall survival (OS) in glioma patients, of which 4 genes were significantly associated with relapse-free survival (RFS) (Figure 1D)
We performed timeROC curves validation of the 4 hub genes, and the results showed that the AUC of C3, TCF12, and IDH1 genes were all greater than 0.6, and the AUC of TP53 was greater than 0.5, further indicating that these four genes have an important role in the prognosis of glioma (Figures S1A-D)
Summary
Glioma is a fatal malignancy with a 5-year survivability rate of only 5%. It is ranked in the thirteenth in terms of cancer-related deaths, accounting for 2.5% of global cancer deaths in 2018 [1]. Tumor vaccines against IDH1 have been successful in slowing the progression of glioblastoma GBM [3]. These vaccines conferred only a limited time survival benefit, the results are promising enough to expand the potential of vaccines associated with GBM. MRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. The purpose of this research was to screen for effective antigens in glioma that could be used for developing mRNA vaccines and to further differentiate the immune subtypes of glioma to create an selection criteria for suitable patients for vaccination
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