文章：

一种与p53依赖性NTRK1激活相关的潜在预后基因标记及其对神经母细胞瘤患者生存率提升的影响

A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients

原文发布日期：8 February 2024

DOI: 10.3390/cancers16040722

类型: Article

开放获取: 是

英文摘要：

Neuroblastoma is the most common extracranial solid tumour in children, comprising close to 10% of childhood cancer-related deaths. We have demonstrated that activation of NTRK1 by TP53 repression of PTPN6 expression is significantly associated with favourable survival in neuroblastoma. The molecular mechanisms by which this activation elicits cell molecular changes need to be determined. This is critical to identify dependable biomarkers for the early detection and prognosis of tumours, and for the development of personalised treatment. In this investigation we have identified and validated a gene signature for the prognosis of neuroblastoma using genes differentially expressed upon activation of the NTRK1-PTPN6-TP53 module. A random survival forest model was used to construct a gene signature, which was then assessed across validation datasets using Kaplan–Meier analysis and ROC curves. The analysis demonstrated that highBASP1,CD9,DLG2,FNBP1,FRMD3,IL11RA,ISGF10,IQCE,KCNQ3, andTOX2,and lowBSG/CD147,CCDC125,GABRB3,GNB2L1/RACK1 HAPLN4,HEBP2, andHSD17B12expression was significantly associated with favourable patient event-free survival (EFS). The gene signature was associated with favourable tumour histology and NTRK1-PTPN6-TP53 module activation. Importantly, all genes were significantly associated with favourable EFS in an independent manner. Six of the signature genes,BSG/CD147,GNB2L1/RACK1,TXNDC5,FNPB1,B3GAT1, andIGSF10, play a role in cell differentiation. Our findings strongly suggest that the identified gene signature is a potential prognostic biomarker and therapeutic target for neuroblastoma patients and that it is associated with neuroblastoma cell differentiation through the activation of the NTRK1-PTPN6-TP53 module.

摘要翻译： 

神经母细胞瘤是儿童最常见的颅外实体瘤，约占儿童癌症相关死亡病例的10%。我们已证实，通过TP53抑制PTPN6表达激活NTRK1与神经母细胞瘤良好预后显著相关。这种激活引发细胞分子变化的分子机制尚待阐明。这对确定可靠的生物标志物以用于肿瘤早期检测、预后评估及个体化治疗开发至关重要。本研究通过筛选NTRK1-PTPN6-TP53模块激活后的差异表达基因，鉴定并验证了神经母细胞瘤预后基因特征谱。采用随机生存森林模型构建基因特征谱，并通过Kaplan-Meier分析和ROC曲线在验证数据集中进行评估。分析表明，高表达的BASP1、CD9、DLG2、FNBP1、FRMD3、IL11RA、ISGF10、IQCE、KCNQ3和TOX2，以及低表达的BSG/CD147、CCDC125、GABRB3、GNB2L1/RACK1、HAPLN4、HEBP2和HSD17B12与患者良好的无事件生存期（EFS）显著相关。该基因特征谱与良好肿瘤组织学特征及NTRK1-PTPN6-TP53模块激活状态相关。重要的是，所有基因均独立显示出与良好EFS的显著关联。特征谱中的六个基因（BSG/CD147、GNB2L1/RACK1、TXNDC5、FNPB1、B3GAT1和IGSF10）在细胞分化过程中发挥作用。我们的研究结果强烈提示，该基因特征谱可作为神经母细胞瘤患者的潜在预后生物标志物和治疗靶点，且通过激活NTRK1-PTPN6-TP53模块与神经母细胞瘤细胞分化过程相关联。

原文链接：

A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients