Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma
Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the e...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1239487/full |
| _version_ | 1797741336459214848 |
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| author | Runhan Zhao Runhan Zhao Yu Jiang Jun Zhang Jun Zhang Yanran Huang Yanran Huang Chuang Xiong Chuang Xiong Zenghui Zhao Zenghui Zhao Tianji Huang Tianji Huang Wei Liu Wei Liu Nian Zhou Nian Zhou Zefang Li Zefang Li Xiaoji Luo Xiaoji Luo Yongli Tang |
| author_facet | Runhan Zhao Runhan Zhao Yu Jiang Jun Zhang Jun Zhang Yanran Huang Yanran Huang Chuang Xiong Chuang Xiong Zenghui Zhao Zenghui Zhao Tianji Huang Tianji Huang Wei Liu Wei Liu Nian Zhou Nian Zhou Zefang Li Zefang Li Xiaoji Luo Xiaoji Luo Yongli Tang |
| author_sort | Runhan Zhao |
| collection | DOAJ |
| description | Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES. |
| first_indexed | 2024-03-12T14:25:21Z |
| format | Article |
| id | doaj.art-7cd91cd69d5245b6bf9cc5436848c1da |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-12T14:25:21Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-7cd91cd69d5245b6bf9cc5436848c1da2023-08-18T07:39:22ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-08-011010.3389/fmed.2023.12394871239487Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcomaRunhan Zhao0Runhan Zhao1Yu Jiang2Jun Zhang3Jun Zhang4Yanran Huang5Yanran Huang6Chuang Xiong7Chuang Xiong8Zenghui Zhao9Zenghui Zhao10Tianji Huang11Tianji Huang12Wei Liu13Wei Liu14Nian Zhou15Nian Zhou16Zefang Li17Zefang Li18Xiaoji Luo19Xiaoji Luo20Yongli Tang21Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaSchool of Public Health, Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, Qianjiang Central Hospital of Chongqing, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaOrthopedic Laboratory of Chongqing Medical University, Chongqing, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaEwing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.https://www.frontiersin.org/articles/10.3389/fmed.2023.1239487/fullprognostic gene signatureEwing sarcomarandom survival forestnecroptosisimmunotherapychemotherapy |
| spellingShingle | Runhan Zhao Runhan Zhao Yu Jiang Jun Zhang Jun Zhang Yanran Huang Yanran Huang Chuang Xiong Chuang Xiong Zenghui Zhao Zenghui Zhao Tianji Huang Tianji Huang Wei Liu Wei Liu Nian Zhou Nian Zhou Zefang Li Zefang Li Xiaoji Luo Xiaoji Luo Yongli Tang Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma Frontiers in Medicine prognostic gene signature Ewing sarcoma random survival forest necroptosis immunotherapy chemotherapy |
| title | Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma |
| title_full | Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma |
| title_fullStr | Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma |
| title_full_unstemmed | Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma |
| title_short | Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma |
| title_sort | development and validation of a novel necroptosis related gene signature for predicting prognosis and therapeutic response in ewing sarcoma |
| topic | prognostic gene signature Ewing sarcoma random survival forest necroptosis immunotherapy chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1239487/full |
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