Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma
Abstract Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-021-01465-w |
| _version_ | 1818572625800069120 |
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| author | Hang Xu Xiaonan Zheng Shiyu Zhang Xianyanling Yi Tianyi Zhang Qiang Wei Hong Li Jianzhong Ai |
| author_facet | Hang Xu Xiaonan Zheng Shiyu Zhang Xianyanling Yi Tianyi Zhang Qiang Wei Hong Li Jianzhong Ai |
| author_sort | Hang Xu |
| collection | DOAJ |
| description | Abstract Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination. |
| first_indexed | 2024-12-15T00:00:07Z |
| format | Article |
| id | doaj.art-d60545b5ae1b45b3b0e2d8cd19c43e32 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-15T00:00:07Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-d60545b5ae1b45b3b0e2d8cd19c43e322022-12-21T22:42:57ZengBMCMolecular Cancer1476-45982021-12-012011710.1186/s12943-021-01465-wTumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinomaHang Xu0Xiaonan Zheng1Shiyu Zhang2Xianyanling Yi3Tianyi Zhang4Qiang Wei5Hong Li6Jianzhong Ai7Institute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityInstitute of Urology, West China Hospital, Sichuan UniversityAbstract Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination.https://doi.org/10.1186/s12943-021-01465-wmRNA vaccineKidney renal clear cell carcinomaImmunotherapyTumor antigensImmune subtypesImmune landscape |
| spellingShingle | Hang Xu Xiaonan Zheng Shiyu Zhang Xianyanling Yi Tianyi Zhang Qiang Wei Hong Li Jianzhong Ai Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma Molecular Cancer mRNA vaccine Kidney renal clear cell carcinoma Immunotherapy Tumor antigens Immune subtypes Immune landscape |
| title | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
| title_full | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
| title_fullStr | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
| title_full_unstemmed | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
| title_short | Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma |
| title_sort | tumor antigens and immune subtypes guided mrna vaccine development for kidney renal clear cell carcinoma |
| topic | mRNA vaccine Kidney renal clear cell carcinoma Immunotherapy Tumor antigens Immune subtypes Immune landscape |
| url | https://doi.org/10.1186/s12943-021-01465-w |
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