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...

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Published in:Frontiers in medicine Vol. 10; p. 1239487
Main Authors: Zhao, Runhan, Jiang, Yu, Zhang, Jun, Huang, Yanran, Xiong, Chuang, Zhao, Zenghui, Huang, Tianji, Liu, Wei, Zhou, Nian, Li, Zefang, Luo, Xiaoji, Tang, Yongli
Format: Journal Article
Language:English
Published: Lausanne Frontiers Media SA 17.08.2023
Frontiers Media S.A
Subjects:
Accuracy
Cancer therapies
Cell culture
Cell death
Chemotherapy
Datasets
Ewing sarcoma
Ewings sarcoma
Gene expression
Genomes
Genomics
Immunotherapy
Kinases
Medical prognosis
Medicine
Metastasis
necroptosis
Nomograms
Patients
prognostic gene signature
random survival forest
Survival analysis
United States > US
ISSN:2296-858X, 2296-858X
Online Access:Get full text
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Summary: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.
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These authors have contributed equally to this work and share first authorship
Edited by: Qi Liu, United States Food and Drug Administration, United States
Reviewed by: Menglun Wang, United States Food and Drug Administration, United States; Shiying Li, Chongqing Medical University, China
ISSN:2296-858X
2296-858X
DOI:10.3389/fmed.2023.1239487