A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction
A 3-Protein Expression Signature of Neuroblastoma for Outcome Prediction
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用于结果预测的神经母细胞瘤的 3 蛋白表达特征
DOI：
10.1097/pas.0000000000001082
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发表时间：
2018-08-01
影响因子：
5.6
通讯作者：
Wu, Yi
中科院分区：
文献类型：
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作者：
Xie, Yi;Xu, Hua;Wu, Yi
神经母细胞瘤（NB）是儿童颅外最常见的实体瘤，其结局截然不同。准确的风险评估有助于预后预测，这对治疗策略决策至关重要。在这项研究中，我们开发了一个3蛋白预测模型，包括神经干细胞标志物Msi 1，神经分化标志物ID 1和增殖标志物增殖细胞核抗原（PCNA），以改善NB患者的临床风险评估。Kaplan-Meier分析显示，在NB患者中，ID 1的低表达和Msi 1和PCNA的高表达与不良预后相关。联合应用这3种标志物构成特征，进一步将NB患者分为不同的风险亚组，有助于获得更准确的预测性能。受试者操作特征分析显示，年龄和Msi1_ID1_PCNA信号对生存预测的能力较经典危险分层系统更有效、更敏感，弥补了年龄预测功能的不足。此外，我们通过免疫组化证实了这3种蛋白在神经母细胞瘤谱组织中的表达，结果显示，与中间节神经母细胞瘤和良性节神经瘤相比，Msi 1和PCNA在NB中的表达增加，而ID 1在NB中的表达水平降低。总之，我们建立了一个强大的风险评估预测模型的基础上简单的免疫组化NB患者的治疗决策。
Neuroblastoma (NB) is the most common extracranial solid tumor in children with contrasting outcomes. Precise risk assessment contributes to prognosis prediction, which is critical for treatment strategy decisions. In this study, we developed a 3-protein predictor model, including the neural stem cell marker Msi1, neural differentiation marker ID1, and proliferation marker proliferating cell nuclear antigen (PCNA), to improve clinical risk assessment of patients with NB. Kaplan-Meier analysis in the microarray data (GSE16476) revealed that low expression of ID1 and high expression of Msi1 and PCNA were associated with poor prognosis in NB patients. Combined application of these 3 markers to constitute a signature further stratified NB patients into different risk subgroups can help obtain more accurate prediction performance. Survival prognostic power of age and Msi1_ID1_PCNA signature by receiver operating characteristics analysis showed that this signature predicted more effectively and sensitively compared with classic risk stratification system, compensating for the deficiency of the prediction function of the age. Furthermore, we validated the expressions of these 3 proteins in neuroblastic tumor spectrum tissues by immunohistochemistry revealed that Msi1 and PCNA exhibited increased expression in NB compared with intermedial ganglioneuroblastoma and benign ganglioneuroma, whereas ID1 levels were reduced in NB. In conclusion, we established a robust risk assessment predictor model based on simple immunohistochemistry for therapeutic decisions of NB patients.