Aierken Yeerfan, Tan Kezhe, Liu Tao, Lv Zhibao
Department of General Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Sci Rep. 2025 Feb 13;15(1):5343. doi: 10.1038/s41598-025-88608-x.
Neuroblastoma (NB) is a malignant tumor originating from the peripheral sympathetic nervous system and high-risk NB patients have a dismal prognosis. Recent studies have underscored the pivotal role of neutrophil extracellular traps (NETs) in the proliferation, metastasis and immune evasion of cancer. To explore the effect of NETs on NB, we have carried out a systematic analysis and showed several findings in the present work. First, expression profiles along with clinical data were analyzed using the training dataset GSE62564 and 36 NETs-related genes were identified to be significantly associated with overall survival. Following LASSO regression analysis, 11 genes were enrolled to construct the NETs signature, which exhibited a robust predictive capability for overall survival with exhibiting high AUC values within the training set. Validation cohorts confirmed a similar predictive efficacy. Next, NB patients were classified into subgroups based on median risk scores and differentially expressed genes were analyzed. Furthermore, the study performed comprehensive analyses encompassing functional enrichment, immune infiltration and drug sensitivity. Enrichment analysis revealed that the high-risk NBs with high-risk score displayed characteristics of oncogenic malignancy, poor prognosis and immunosuppression. Notably, the risk score exhibited a strong correlation with infiltration levels of various immune cells and the sensitivity to anti-cancer drugs, and was further recognized as an independent prognostic factor for NB patients. In summary, our study elucidates a novel NETs-related gene signature comprising 11 genes, which serves a reliable predictor for NB prognosis.
神经母细胞瘤(NB)是一种起源于外周交感神经系统的恶性肿瘤,高危NB患者的预后较差。最近的研究强调了中性粒细胞胞外陷阱(NETs)在癌症增殖、转移和免疫逃逸中的关键作用。为了探究NETs对NB的影响,我们进行了系统分析,并在本研究中展示了一些发现。首先,使用训练数据集GSE62564分析了表达谱和临床数据,确定了36个与NETs相关的基因与总生存期显著相关。经过LASSO回归分析,纳入11个基因构建NETs特征,该特征在训练集中对总生存期具有强大的预测能力,AUC值较高。验证队列证实了类似的预测效果。接下来,根据中位风险评分将NB患者分为亚组,并分析差异表达基因。此外,该研究还进行了包括功能富集、免疫浸润和药物敏感性在内的综合分析。富集分析显示,高风险评分的高危NB具有致癌恶性、预后不良和免疫抑制的特征。值得注意的是,风险评分与各种免疫细胞的浸润水平和对抗癌药物的敏感性密切相关,并被进一步确认为NB患者的独立预后因素。总之,我们的研究阐明了一个由11个基因组成的与NETs相关的新基因特征,它是NB预后的可靠预测指标。