Li Shihao, Hou Yanli, Zhang Lina, Zhang Haiyang, Wang Congcong
Department of Orthopedics, Zibo Central Hospital West Campus, Zhangdian District, Zibo, 255036, Shandong Province, People's Republic of China.
Department of Hand & Foot Surgery, Zibo Central Hospital, Zhangdian District, Zibo, 255036, Shandong Province, People's Republic of China.
Sci Rep. 2025 Jul 8;15(1):24523. doi: 10.1038/s41598-025-10277-7.
Ewing sarcoma (EWS) is a rare bone cancer that is most usually detected in children. Neutrophil extracellular traps (NETs) are closely related to the prognosis of cancer, but the significance of NET-related features in EWS remains uncertain. We constructed a NET signature utilizing four crucial NET-related genes in EWS to forecast prognosis and investigate the potential immunological value of this signature in EWS. EWS data were collected from the International Cancer Genome Consortium and Gene Expression Omnibus databases. We identified the subtypes mediated by NET-related genes in EWS and analyzed the function infiltration and immune signature of NET-related subtypes in EWS. The expression levels of proteins in EWS cells were detected via western blotting analysis. NET could distinguish EWS patients into two NET-related subtypes: C1 and C2. EWS patients with the C1 subtype exhibited a more unfavorable prognosis and higher levels of TIDE and T cell dysfunction when compared to individuals with the C2 subtype. C1 and C2 subtypes had different immune characteristics. A NET-related prognostic model including AKT1, MAPK3, ATG7, and SELPLG was established to predict the prognosis of EWS patients. The risk score model was an independent prognostic factor for EWS, and high-risk EWS patients exhibited significantly inferior prognosis. AKT1 and ATG7 expression was significantly increased in EWS samples. The protein levels of AKT1 and ATG7 were increased in EWS cells, while the protein levels of SELPLG was decreased. The NET-related prognostic model is a critical biomarker for predicting prognosis, defining molecular subtypes, and describing immune signatures in patients with EWS.
尤因肉瘤（EWS）是一种罕见的骨癌，最常发生于儿童。中性粒细胞胞外陷阱（NETs）与癌症预后密切相关，但NET相关特征在EWS中的意义仍不明确。我们利用EWS中四个关键的NET相关基因构建了一个NET特征，以预测预后并研究该特征在EWS中的潜在免疫价值。EWS数据来自国际癌症基因组联盟和基因表达综合数据库。我们确定了EWS中由NET相关基因介导的亚型，并分析了EWS中NET相关亚型的功能浸润和免疫特征。通过蛋白质免疫印迹分析检测EWS细胞中蛋白质的表达水平。NET可将EWS患者分为两种NET相关亚型：C1和C2。与C2亚型患者相比，C1亚型的EWS患者预后更差，TIDE和T细胞功能障碍水平更高。C1和C2亚型具有不同的免疫特征。建立了一个包括AKT1、MAPK3、ATG7和SELPLG的NET相关预后模型，以预测EWS患者的预后。风险评分模型是EWS的一个独立预后因素，高危EWS患者的预后明显较差。EWS样本中AKT1和ATG7的表达显著增加。EWS细胞中AKT1和ATG7的蛋白质水平升高，而SELPLG的蛋白质水平降低。NET相关预后模型是预测EWS患者预后、定义分子亚型和描述免疫特征的关键生物标志物。
