A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer
BackgroundTP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC.MethodsRNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) an...
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| Format: | Article |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.590618/full |
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| author | Xiangkun Wu Xiangkun Wu Daojun Lv Daojun Lv Chao Cai Chao Cai Zhijian Zhao Zhijian Zhao Ming Wang Ming Wang Wenzhe Chen Wenzhe Chen Yongda Liu Yongda Liu |
| author_facet | Xiangkun Wu Xiangkun Wu Daojun Lv Daojun Lv Chao Cai Chao Cai Zhijian Zhao Zhijian Zhao Ming Wang Ming Wang Wenzhe Chen Wenzhe Chen Yongda Liu Yongda Liu |
| author_sort | Xiangkun Wu |
| collection | DOAJ |
| description | BackgroundTP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC.MethodsRNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations.ResultsA total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti–PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use.ConclusionTIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential. |
| first_indexed | 2024-12-23T04:22:27Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T04:22:27Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-eb2f721ef66c407f83147d5da42b384b2022-12-21T18:00:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.590618590618A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder CancerXiangkun Wu0Xiangkun Wu1Daojun Lv2Daojun Lv3Chao Cai4Chao Cai5Zhijian Zhao6Zhijian Zhao7Ming Wang8Ming Wang9Wenzhe Chen10Wenzhe Chen11Yongda Liu12Yongda Liu13Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaDepartment of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, ChinaBackgroundTP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC.MethodsRNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations.ResultsA total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti–PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use.ConclusionTIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential.https://www.frontiersin.org/articles/10.3389/fimmu.2020.590618/fullmuscle-invasive bladder cancerTP53 mutationimmune prognostic signaturenomogramthe cancer genome atlas (TCGA) and gene expression omnibus (GEO) database |
| spellingShingle | Xiangkun Wu Xiangkun Wu Daojun Lv Daojun Lv Chao Cai Chao Cai Zhijian Zhao Zhijian Zhao Ming Wang Ming Wang Wenzhe Chen Wenzhe Chen Yongda Liu Yongda Liu A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer Frontiers in Immunology muscle-invasive bladder cancer TP53 mutation immune prognostic signature nomogram the cancer genome atlas (TCGA) and gene expression omnibus (GEO) database |
| title | A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer |
| title_full | A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer |
| title_fullStr | A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer |
| title_full_unstemmed | A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer |
| title_short | A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer |
| title_sort | tp53 associated immune prognostic signature for the prediction of overall survival and therapeutic responses in muscle invasive bladder cancer |
| topic | muscle-invasive bladder cancer TP53 mutation immune prognostic signature nomogram the cancer genome atlas (TCGA) and gene expression omnibus (GEO) database |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.590618/full |
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