Hong Peng, Hu Zaihong, Lin Jie, Cui Kongkong, Gao Zhiqiang, Tian Xiaomao, Shi Qinlin, Lin Tao, Wei Guanghui
Department of Urology, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, China.
Department of Urology, Children's Hospital of Chongqing Medical University; National Clinical Research Center for Child Health and Disorders; Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Structural Birth Defect and Reconstruction, China.
Int J Biol Macromol. 2024 Dec;282(Pt 4):137045. doi: 10.1016/j.ijbiomac.2024.137045. Epub 2024 Oct 31.
Neuroblastoma (NB), a common and highly lethal malignant disease in pediatrics, still lacks an effective therapeutic approach that addresses all conditions. Immunogenic Cell Death (ICD) plays a crucial role in tumor cell death and triggers a potent anti-tumor immune response. In this study, we report an ICD-related index (ICDR-Index) in NB through various machine learning methodologies, utilizing bulk transcriptome data from 1244 NB samples and 16 scRNA-seq datasets. Our results showed that the ICDR-Index could accurately identify different risk subtypes of patients with NB and provide predictive value for prognosis. Importantly, we found that high-risk patients with NB exhibited significantly poor overall survival (OS) rates, adverse clinical phenotypes, poor immune cell infiltration, and low sensitivity to immunotherapy. Furthermore, we identified ELAVL3 as a key gene within the ICDR-Index, where high expression levels were associated with malignancy and poor OS in NB. Additionally, targeted silencing of ELAVL3 down-regulated MYCN gene expression and reduced the malignancy of NB cells. Notably, the si-ELAVL3-transfected NB cells enhanced the anti-tumor activity of NK cells. Collectively, this study offers avenues for predicting the risk stratification of patients with NB and reveals a potential mechanism by which ELAVL3 regulates NB cell death.
神经母细胞瘤（NB）是儿科常见且致死率高的恶性疾病，目前仍缺乏能应对所有情况的有效治疗方法。免疫原性细胞死亡（ICD）在肿瘤细胞死亡中起关键作用，并引发强大的抗肿瘤免疫反应。在本研究中，我们利用来自1244个NB样本的批量转录组数据和16个单细胞RNA测序（scRNA-seq）数据集，通过各种机器学习方法报告了NB中的一种ICD相关指数（ICDR-指数）。我们的结果表明，ICDR-指数可以准确识别NB患者的不同风险亚型，并为预后提供预测价值。重要的是，我们发现NB高危患者的总生存率（OS）显著较差、临床表型不良、免疫细胞浸润不佳且对免疫治疗敏感性低。此外，我们确定ELAVL3是ICDR-指数中的关键基因，其高表达水平与NB中的恶性程度和不良OS相关。此外，靶向沉默ELAVL3可下调MYCN基因表达并降低NB细胞的恶性程度。值得注意的是，经si-ELAVL3转染的NB细胞增强了NK细胞的抗肿瘤活性。总体而言，本研究为预测NB患者的风险分层提供了途径，并揭示了ELAVL3调节NB细胞死亡的潜在机制。
