神经母细胞瘤（NB）具有明显的异质性，是儿童中最常见的颅外实体瘤。线粒体的状态和功能对于调节 NB 细胞行为至关重要。而线粒体相关基因（MRG）在NB中的重要性仍然缺乏关键知识。本研究利用共识聚类和机器学习算法来构建和验证NB中MRG相关的签名。采用单细胞数据分析和实验验证来表征 FEN1 在 NB 细胞中的关键作用。MRG 有助于将 NB 患者分为 2 个具有相当大差异的不同簇。构建的 MRGs 相关特征及其定量指标 mtScore 和 mtRisk 有效地表征了 MRGs 相关患者群。值得注意的是，MRGs 相关特征在预测 NB 患者预后方面优于 MYCN，并且擅长代表肿瘤微环境 (TME)、肿瘤细胞干性以及对化疗药物顺铂、拓扑替康和伊立替康的敏感性。 FEN1 被认为是 MRG 相关特征中贡献最大的基因，被发现在 NB 细胞和 TME 之间的通讯以及 NB 细胞的发育轨迹中发挥着至关重要的作用。实验验证证实了 FEN1 对 NB 细胞增殖、凋亡、细胞周期和侵袭性具有显着影响。本研究中开发的 MRGs 相关特征为评估 NB 患者预后、免疫浸润、干性和化疗敏感性提供了一种新颖的预测工具。我们的研究结果揭示了 FEN1 在 NB 中的关键功能，表明其作为治疗靶点的潜力。版权所有 © 2024 Wang、Tan、Jin、Li、Yang、Jia、Xia、Gong、Dong 和 Zhao。

Neuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge.This study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells.MRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1's significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness.The MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target.Copyright © 2024 Wang, Tan, Jin, Li, Yang, Jia, Xia, Gong, Dong and Zhao.