Identification of three tumor antigens and immune subtypes for mRNA vaccine development in diffuse glioma

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.

Identification of PIK3CG as a hub in septic myocardial injury using network pharmacology and weighted gene co‐expression network analysis

“…2.2 | Identification of core genes related to SV, CO, sepsis score, and group in the weighted co-expression network WGCNA is generally used to identify modules and candidate marker genes related to external sample traits and has been successfully performed in various biological entities, such as cancer and mouse genome. 21,22 Here in this study, WGCNA was applied to quest genes related with biometric, plasma and echocardiographic parameters of septic mice (see Section 5 for details), in an effort to identify core candidate targets by structuring a scale-free gene co-expression network.…”

Identification of tumor antigens and immune subtypes in lung squamous cell carcinoma for mRNA vaccine development

“…We speculated that this may be due to the different EGFR mutation landscapes between the 2 groups (see Figure 6I,6J). Thus, the treatment of LUSC should focus on the CPA3 [ 20] ZNF716 [ 24] FBXW7 [ 25] SAGE1 [27] ARID1A [ 29] RASA1 [ 30] SLCO1B1 [ 32] RB1 [ 35] NF1 [ 43] KEAP1 [ 48] PTEN [ 51] PTEN [ 51] KEAP1 [ 48] NF1 [ 43] RB1 [ 35] SLCO1B1 [ 32] RASA1 [ 30] ARID1A [ 29] SAGE1 [27] FBXW7 [ 25] ZNF716 [ 24] CPA3 [ 20] CUL3 [ 19] Altered in 477 (97.15%) of 491 samples.…”

Immune repertoire analysis of normal Chinese donors at different ages

“…In recent years, with the rapid development of HTS technology, IR has been widely used in disease‐related research. 17 , 18 , 19 , 20 , 21 , 22 , 23 One study found that there were differences in the use of V and J genes in both β and IGH chains in patients with non‐small cell lung cancer (NSCLC). It was found that the clonality and diversity of the TCR repertoire in the early recurrence patients were increased and decreased, respectively, compared to the early non‐recurrence patients.…”

“…[14][15][16] In recent years, with the rapid development of HTS technology, IR has been widely used in disease-related research. [17][18][19][20][21][22][23] One study found that there were differences in the use of V and J genes in both β and IGH chains in patients with non-small cell lung cancer (NSCLC).…”

“…[31][32][33][34] Dimer-avoided multiplex PCR (Dam-PCR) can be used to amplify all seven chains of the IR in the same PCR reaction system under the same conditions, with unique molecular IDs (UMIs), which can reduce the amplification bias and directly compare the gene expression level quantitatively. In this study, 16 normal Chinese participants were divided into two groups based on age: Group 1 (ages [19][20][21][22][23][24][25][26][27][28][29][30] and Group 2 (ages 50-67), with eight participants in each group. Peripheral blood samples from the participants were collected, RNA was extracted and Dam-PCR combined with HTS was used to analyze the IR of each participant.…”