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Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development
BACKGROUND: mRNA 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-suita...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263198/ https://www.ncbi.nlm.nih.gov/pubmed/35814377 http://dx.doi.org/10.3389/fonc.2022.921711 |
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author | Wang, Guixin Gao, Yukui Chen, Yanzhuo Wang, Keruo Zhang, Shicheng Li, Gang |
author_facet | Wang, Guixin Gao, Yukui Chen, Yanzhuo Wang, Keruo Zhang, Shicheng Li, Gang |
author_sort | Wang, Guixin |
collection | PubMed |
description | BACKGROUND: mRNA 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. METHODS: Clinical 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. RESULTS: AP2S1, 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. CONCLUSIONS: AP2S1, 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. |
format | Online Article Text |
id | pubmed-9263198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92631982022-07-09 Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development Wang, Guixin Gao, Yukui Chen, Yanzhuo Wang, Keruo Zhang, Shicheng Li, Gang Front Oncol Oncology BACKGROUND: mRNA 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. METHODS: Clinical 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. RESULTS: AP2S1, 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. CONCLUSIONS: AP2S1, 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. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263198/ /pubmed/35814377 http://dx.doi.org/10.3389/fonc.2022.921711 Text en Copyright © 2022 Wang, Gao, Chen, Wang, Zhang and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wang, Guixin Gao, Yukui Chen, Yanzhuo Wang, Keruo Zhang, Shicheng Li, Gang Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title | Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title_full | Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title_fullStr | Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title_full_unstemmed | Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title_short | Identification of Novel Tumor Antigens and the Immune Landscapes of Bladder Cancer Patients for mRNA Vaccine Development |
title_sort | identification of novel tumor antigens and the immune landscapes of bladder cancer patients for mrna vaccine development |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263198/ https://www.ncbi.nlm.nih.gov/pubmed/35814377 http://dx.doi.org/10.3389/fonc.2022.921711 |
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