神经母细胞瘤是儿童中最常见的颅外实体瘤。尽管现有疗法取得了重大进展，但患有耐药性和/或复发性神经母细胞瘤的儿童前景黯淡，5 年生存率低于 20%。因此，通过开发和表征临床相关模型来解决复发性肿瘤生物学问题是寻找神经母细胞瘤可靶向脆弱性的首要任务。使用匹配的顺铂敏感性 KellyLuc 和耐药性 KellyCis83Luc 细胞系，我们开发了顺铂耐药性转移性 MYCN 扩增神经母细胞瘤模型。 KellyCis83Luc 组每只小鼠的平均转移瘤数量显着高于 KellyLuc 组。绝大多数部位被证实有淋巴结转移。它们的淋巴结转移值的硬度特征在患者样本报告的范围内。免疫肿瘤基因的靶向转录组分析发现肿瘤坏死因子受体超家族成员 4 (TNFRSF4) 是一个显着失调的不依赖于 MYCN 的基因。重要的是，在肿瘤细胞而不是淋巴细胞中发现了差异的 TNFRSF4 表达。 TNFRSF4低表达与神经母细胞瘤的不良预后指标相关，例如诊断时的年龄、分期和风险分层，并且与神经母细胞瘤的无事件生存率和总生存率降低显着相关。因此，TNFRSF4低表达是神经母细胞瘤生存的独立预后因素。版权所有：©2024 Murphy et al.这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma.Copyright: © 2024 Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.