BackgroundmRNA vaccines are a novel technology that provide a potential strategy for cancer treatment. However, few studies exist that are focused on the application and development of mRNA vaccines in bladder cancer (BLCA). Therefore, this study filtered candidate antigens and specific mRNA-suitable populations in BLCA via comprehensive multi-omics analysis.MethodsClinical information, follow-up information, and gene expression profiles were obtained from the TCGA and GEO databases. Somatic mutation and DNA copy number variation of BLCA were visualized by cBioPortal. Significant survival genes were analyzed by GEPIA2. TIMER was used to evaluate the connection between candidate antigens and infiltration of antigen-presenting cells. Consensus clustering analysis was performed to identify immune subtypes using the ConsensusClusterPlus package. The Monocle package was used to visualize the immune landscapes of each BLCA patient. Weighted gene co-expression network analysis (WGCNA) was used to identify key genes for mRNA vaccines.ResultsAP2S1, P3H4, and RAC3 were identified as candidate tumor-specific antigens for BLCA. Three immune subtypes were classified based on immune-related gene expression profiles. Patients with the BCS2 subtype were characterized as immune “cold” and exhibited upregulation of immunogenic cell death modulators, whereas patients with BCS1 and BCS3 were immune “hot” and had upregulation of immune checkpoints. Interestingly, patients with the BCS2 subtype had a better prognosis than other subtypes. The immune landscapes of each patient were visualized and revealed the heterogeneity within the BCS1 subtype. Finally, 13 key immune genes were identified.ConclusionsAP2S1, P3H4, and RAC3 were identified as candidate tumor-specific antigens, and patients with the BCS2 and BCS1A subtypes were identified as candidate populations for mRNA vaccines. In summary, this study provides novel insights and a theoretical basis for mRNA vaccine development in BLCA and other malignancies.
Background: Messenger ribonucleic acid (mRNA) vaccine has been considered as a potential therapeutic strategy and the next research hotspot, but their efficacy against prostate adenocarcinoma (PRAD) remains undefined. This study aimed to find potential antigens of PRAD for mRNA vaccine development and identify suitable patients for vaccination through immunophenotyping.Methods: Gene expression profiles and clinical information were obtained from TCGA and ICGC. GEPIA2 was used to calculate the prognostic index of the selected antigens. The genetic alterations were compared on cBioPortal and the correlation between potential antigen and immune infiltrating cells was explored by TIMER. ConsensusClusterPlus was used to construct a consistency matrix, and identify the immune subtypes. Graph learning-based dimensional reduction was performed to depict immune landscape. Boruta algorithm and LASSO logistic analysis were used to screen PRAD patients who may benefit from mRNA vaccine.Results: Seven potential tumor antigens selected were significantly positively associated with poor prognosis and the antigen-presenting immune cells (APCs) in PRAD, including ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, and UPP1. Five immune subtypes of PRAD were identified by differential molecular, cellular, and clinical characteristics in both cohorts. C3 and C5 had immune “hot” and immunosuppressive phenotype, On the contrary, C1&C2 had immune “cold” phenotype. Finally, the immune landscape characterization showed the immune heterogeneity among patients with PRAD.Conclusions: ADA, FYN, HDC, NFKBIZ, RASSF4, SLC6A3, and UPP1 are potential antigens for mRNA vaccine development against PRAD, and patients in type C1 and C2 are suitable for vaccination.
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