Ye Guogang, Wang Yue
Department of General Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Evol Bioinform Online. 2022 Aug 26;18:11769343221120960. doi: 10.1177/11769343221120960. eCollection 2022.
Neuroblastoma (NB) is the most common solid malignancy in children. MYCN gene amplification is the most relevant genetic alteration in patients with NB and is associated with poor prognosis. Autophagy plays specific roles in the occurrence, development, and progression of NB. Here, we aimed to identify and assess the prognostic effects of autophagy-related genes (ARGs) in patients with NB and MYCN gene amplification. Differentially expressed ARGs were identified in patients with NB with and without MYCN gene amplification, and the ARG expression patterns and related clinical data from the Therapeutically Applicable Research to Generate Effective Treatments database were used as the training cohort. Least absolute shrinkage and selection operator analyses were used to identify prognostic ARGs associated with event-free survival (EFS), and a prognostic risk score model was developed. Model performance was assessed using the Kaplan-Meier method and receiver operating characteristic (ROC) curves. The prognostic ARG mode l was verified using the validation cohort dataset, GSE49710. Finally, a nomogram was constructed by combining the ARGbased risk score with clinicopathological factors. Three ARGs (GABARAPL1, NBR1, and PINK1) were selected to build a prognostic risk score model. The EFS in the low-risk group was significantly better than that in the high-risk group in both the training and validation cohorts. A nomogram incorporating the prognostic risk score, age, and International Neuroblastoma Staging System stage showed a favorable predictive ability for EFS rates according to the area under the ROC curve at 3 years (AUC = 0.787) and 5 years (AUC = 0.787). The nomogram demonstrated good discrimination and calibration. Our risk score model for the 3 ARGs can be used as an independent prognostic factor in patients with NB and MYCN gene amplification. The model can accurately predict the 3- and 5-year survival rates.
神经母细胞瘤（NB）是儿童最常见的实体恶性肿瘤。MYCN基因扩增是NB患者中最相关的基因改变，与预后不良相关。自噬在NB的发生、发展和进展中发挥着特定作用。在此，我们旨在识别和评估自噬相关基因（ARG）对NB和MYCN基因扩增患者的预后影响。在有和没有MYCN基因扩增的NB患者中识别差异表达的ARG，并将来自“生成有效治疗的治疗性应用研究”数据库的ARG表达模式和相关临床数据用作训练队列。使用最小绝对收缩和选择算子分析来识别与无事件生存期（EFS）相关的预后ARG，并建立预后风险评分模型。使用Kaplan-Meier方法和受试者工作特征（ROC）曲线评估模型性能。使用验证队列数据集GSE49710验证预后ARG模型。最后，通过将基于ARG的风险评分与临床病理因素相结合构建列线图。选择三个ARG（GABARAPL1、NBR1和PINK1）构建预后风险评分模型。在训练和验证队列中，低风险组的EFS均显著优于高风险组。结合预后风险评分、年龄和国际神经母细胞瘤分期系统分期的列线图在3年（AUC = 0.787）和5年（AUC = 0.787）时根据ROC曲线下面积显示出对EFS率的良好预测能力。列线图显示出良好的区分度和校准度。我们针对这三个ARG的风险评分模型可作为NB和MYCN基因扩增患者的独立预后因素。该模型可以准确预测3年和5年生存率。
