Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer
BackgroundBladder cancer (BLCA) is one of the most prevalent urinary system malignancies, with high mortality and recurrence. The present study aimed to identify potential tumor antigens for mRNA vaccines in BLCA and patient subtypes suitable for different immunotherapy.MethodsGene expression profil...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014638/full |
| _version_ | 1811179168358989824 |
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| author | Xin Zhang Xin Zhang Xin Zhang Yanlong Zhang Li Zhao Jiayu Wang Jiayu Wang Jiaxing Li Jiaxing Li Xi Wang Xi Wang Xi Wang Min Zhang Min Zhang Min Zhang Xiaopeng Hu Xiaopeng Hu |
| author_facet | Xin Zhang Xin Zhang Xin Zhang Yanlong Zhang Li Zhao Jiayu Wang Jiayu Wang Jiaxing Li Jiaxing Li Xi Wang Xi Wang Xi Wang Min Zhang Min Zhang Min Zhang Xiaopeng Hu Xiaopeng Hu |
| author_sort | Xin Zhang |
| collection | DOAJ |
| description | BackgroundBladder cancer (BLCA) is one of the most prevalent urinary system malignancies, with high mortality and recurrence. The present study aimed to identify potential tumor antigens for mRNA vaccines in BLCA and patient subtypes suitable for different immunotherapy.MethodsGene expression profiles, mutation data, methylation data, and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases. Immunohistochemical staining of microarrays was performed to assess protein expression levels of IGF2BP2 and MMP9. Differential gene analysis, survival analysis, correlation analysis, consensus clustering analysis, and immune cell infiltration analysis were conducted using R software. Finally, the R package “immcluster” was used based on Combat and eXtreme Gradient Boosting algorithms to predict immune clusters of BLCA samples.ResultsTwo mutated, amplified, and over-expressed tumor antigens, IGF2BP2 and MMP9, were found to be associated with clinical outcomes and the abundance of antigen-presenting cells (APCs). Subsequently, three immune subtypes (BIS1, BIS2, and BIS3) were defined in the BLCA cohort. BIS3 subtype exhibited an “active” immune phenotype, while BIS1 and BIS2 subtypes have a “suppressive” immune phenotype. Patients in BIS1 and BIS2 had a poor prognosis compared to BIS3. BIS3 had a higher score in checkpoints or immunomodulators (CP) and immunophenoscore (IPS), while BIS1 and BIS2 scored higher in major histocompatibility complex-related molecules (MHC molecules). Meanwhile, BIS2 and BIS3 had a significantly higher tumor mutational burden (TMB) compared to patients with BIS1. Finally, the “immcluster” package was applied to the dataset, which has been shown to accurately predict the immune subtypes of BLCA samples in many cohorts.ConclusionsIGF2BP2 and MMP9 were potential antigens for developing mRNA vaccines against BLCA. The results in the present study suggested that immunotherapy targeting these two antigens would be suitable for patients falling under the BIS2 subtype. R package “immcluster” could assist in screening suitable BLCA patients for antitumor therapy. |
| first_indexed | 2024-04-11T06:31:20Z |
| format | Article |
| id | doaj.art-171005501e2844f395a0bf68391de140 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T06:31:20Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-171005501e2844f395a0bf68391de1402022-12-22T04:40:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10146381014638Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancerXin Zhang0Xin Zhang1Xin Zhang2Yanlong Zhang3Li Zhao4Jiayu Wang5Jiayu Wang6Jiaxing Li7Jiaxing Li8Xi Wang9Xi Wang10Xi Wang11Min Zhang12Min Zhang13Min Zhang14Xiaopeng Hu15Xiaopeng Hu16Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaInstitute of Infectious Diseases, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaSchool of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaInstitute of Infectious Diseases, Beijing Key Laboratory of Emerging Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaDepartment of Immunology, School of Basic Medical Sciences, Department of Oncology, Capital Medical University, Beijing, ChinaBeijing Institute of Infectious Diseases, Beijing, ChinaDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaDepartment of Research Ward, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaDepartment of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, ChinaInstitute of Urology, Capital Medical University, Beijing, ChinaBackgroundBladder cancer (BLCA) is one of the most prevalent urinary system malignancies, with high mortality and recurrence. The present study aimed to identify potential tumor antigens for mRNA vaccines in BLCA and patient subtypes suitable for different immunotherapy.MethodsGene expression profiles, mutation data, methylation data, and corresponding clinical information were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases. Immunohistochemical staining of microarrays was performed to assess protein expression levels of IGF2BP2 and MMP9. Differential gene analysis, survival analysis, correlation analysis, consensus clustering analysis, and immune cell infiltration analysis were conducted using R software. Finally, the R package “immcluster” was used based on Combat and eXtreme Gradient Boosting algorithms to predict immune clusters of BLCA samples.ResultsTwo mutated, amplified, and over-expressed tumor antigens, IGF2BP2 and MMP9, were found to be associated with clinical outcomes and the abundance of antigen-presenting cells (APCs). Subsequently, three immune subtypes (BIS1, BIS2, and BIS3) were defined in the BLCA cohort. BIS3 subtype exhibited an “active” immune phenotype, while BIS1 and BIS2 subtypes have a “suppressive” immune phenotype. Patients in BIS1 and BIS2 had a poor prognosis compared to BIS3. BIS3 had a higher score in checkpoints or immunomodulators (CP) and immunophenoscore (IPS), while BIS1 and BIS2 scored higher in major histocompatibility complex-related molecules (MHC molecules). Meanwhile, BIS2 and BIS3 had a significantly higher tumor mutational burden (TMB) compared to patients with BIS1. Finally, the “immcluster” package was applied to the dataset, which has been shown to accurately predict the immune subtypes of BLCA samples in many cohorts.ConclusionsIGF2BP2 and MMP9 were potential antigens for developing mRNA vaccines against BLCA. The results in the present study suggested that immunotherapy targeting these two antigens would be suitable for patients falling under the BIS2 subtype. R package “immcluster” could assist in screening suitable BLCA patients for antitumor therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014638/fullmRNA vaccinetumor antigenbladder cancerimmune subtypestumor immune infiltration |
| spellingShingle | Xin Zhang Xin Zhang Xin Zhang Yanlong Zhang Li Zhao Jiayu Wang Jiayu Wang Jiaxing Li Jiaxing Li Xi Wang Xi Wang Xi Wang Min Zhang Min Zhang Min Zhang Xiaopeng Hu Xiaopeng Hu Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer Frontiers in Immunology mRNA vaccine tumor antigen bladder cancer immune subtypes tumor immune infiltration |
| title | Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer |
| title_full | Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer |
| title_fullStr | Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer |
| title_full_unstemmed | Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer |
| title_short | Exploitation of tumor antigens and construction of immune subtype classifier for mRNA vaccine development in bladder cancer |
| title_sort | exploitation of tumor antigens and construction of immune subtype classifier for mrna vaccine development in bladder cancer |
| topic | mRNA vaccine tumor antigen bladder cancer immune subtypes tumor immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014638/full |
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