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基于转录因子活动的分层揭示了神经母细胞瘤中预后亚型和免疫格局

Mingyou Gao¹, Xin Li², Yuren Xia¹

¹Department of Pediatric Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China.

Translational pediatrics

|January 8, 2026

概括

高危神经母细胞瘤 (NB) 的生存率很差. 一个新的转录因子 (TF) 评分可以识别攻击性NB亚型,并预测免疫治疗反应,改善风险分层超出传统标记.

科学领域:

在瘤学瘤学.
基因组学就是基因组学.
免疫学免疫学免疫学

背景情况:

高风险神经母细胞瘤 (NB) 长期存活率很低 (<50%),尽管目前的治疗方法.
传统的风险因素 (年龄,阶段,MYCN状态) 并不能完全捕捉到NB的攻击性或免疫逃避机制.
转录因子 (TF) 活动概况可能会揭示临床相关的NB亚型.

研究的目的:

在NB中描述TF活动.
开发和验证NB的基于TF的预后得分.
调查TF活动与瘤免疫微环境之间的关联.

主要方法:

在498个初级NB瘤中,使用decoupleR和OmniPath regulon推断了TF活动.
使用共识聚类和PCA对与生存相关的TFs创建了一个连续的TF_score.
在TF_score层中分析了免疫透和免疫疗法反应替代物 (IPS,TIDE).
开发并使用外部队列和单细胞RNA-seq数据验证了一个预后名录.

主要成果:

确定了两种NB亚型;一个与更差的预后,MYCN放大和更高的茎度有关.
与MYCN放大和瘤阶段相比,TF_score显示出更好的生存预测.
高TF_score与减少的免疫透和较低的预测免疫治疗反应相关.
一个经过验证的nomogram整合了TF_score,阶段和MYCN放大用于风险分层.

结论:

TF活动概况为NB提供了强大的分层,整合了临床和免疫特征.
这种方法为TF驱动的NB生物学提供了洞察力.
这些发现对开发向疗法和免疫治疗策略有影响.

关键词:

神经母细胞瘤 (NB) 是一个免疫系统的景观.预后生物标志物预后生物标志物风险分层的分层是风险分层.转录因子活动 (TF活动)

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