Development and validation of a novel necroptosis-related gene signature for predicting prognosis and therapeutic response in Ewing sarcoma

作者全名："Zhao, Runhan; Jiang, Yu; Zhang, Jun; Huang, Yanran; Xiong, Chuang; Zhao, Zenghui; Huang, Tianji; Liu, Wei; Zhou, Nian; Li, Zefang; Luo, Xiaoji; Tang, Yongli"

作者地址："[Zhao, Runhan; Zhang, Jun; Huang, Yanran; Xiong, Chuang; Zhao, Zenghui; Huang, Tianji; Liu, Wei; Zhou, Nian; Li, Zefang; Luo, Xiaoji; Tang, Yongli] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China; [Zhao, Runhan; Zhang, Jun; Huang, Yanran; Xiong, Chuang; Zhao, Zenghui; Huang, Tianji; Liu, Wei; Zhou, Nian; Luo, Xiaoji] Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China; [Jiang, Yu] Chongqing Med Univ, Sch Publ Hlth, Chongqing, Peoples R China; [Li, Zefang] Qianjiang Cent Hosp Chongqing, Dept Orthoped, Chongqing, Peoples R China"

通信作者："Li, ZF; Luo, XJ; Tang, YL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing, Peoples R China.; Luo, XJ (通讯作者)，Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China.; Li, ZF (通讯作者)，Qianjiang Cent Hosp Chongqing, Dept Orthoped, Chongqing, Peoples R China."

来源：FRONTIERS IN MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001059150500001

JCR分区：Q1

影响因子：3.1

年份：2023

卷号：10

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：prognostic gene signature; Ewing sarcoma; random survival forest; necroptosis; immunotherapy; chemotherapy

摘要："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."

基金机构：This research was supported by National Natural Science Foundation of China (Grant No. 81873998) and Chongqing Young and Middle-aged Medical High-end Talent Studio (Grant No. cstc2022ycjh-bgzxm0103). [cstc2022ycjh-bgzxm0103]; National Natural Science Foundation of China; Chongqing Young and Middle-aged Medical High-end Talent Studio; [81873998]

基金资助正文：This research was supported by National Natural Science Foundation of China (Grant No. 81873998) and Chongqing Young and Middle-aged Medical High-end Talent Studio (Grant No. cstc2022ycjh-bgzxm0103).