Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study
Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study
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DOI：
10.3390/cancers11101476
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发表时间：
2019-10-01
期刊：
影响因子：
5.2
通讯作者：
Varesio, Luigi
中科院分区：
文献类型：
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作者：
Morini, Martina;Cangelosi, Davide;Varesio, Luigi
尽管进行了强化治疗，但50%的高危神经母细胞瘤（HR-NB）儿童仍死于疾病。通过目前的试验评估HR疾病儿童新治疗方法的疗效通常取决于对诱导化疗的反应不足，使用成像方式进行评估。在这项研究中，我们试图确定可能在简单血液样本中检测到的循环生物标志物，以预测患者对诱导化疗的反应。由于肿瘤细胞释放的外泌体可以驱动肿瘤生长和化疗耐药性，我们测试了血液中的外泌体microRNA（exo-miRNAs）可能预测对诱导化疗的反应的假设。比较诱导化疗前后从接受HR-NBL-1/SIOPEN治疗的儿童中收集的血浆样本中的exo-miRNAs表达谱，以鉴定可以区分不良反应者和良好反应者的三种exo-miRs特征。exo-miRNAs表达也提供了一个预测HR-NB患者预后良好或不良的化疗耐药指数。
Despite intensive treatment, 50% of children with high-risk neuroblastoma (HR-NB) succumb to their disease. Progression through current trials evaluating the efficacy of new treatments for children with HR disease usually depends on an inadequate response to induction chemotherapy, assessed using imaging modalities. In this study, we sought to identify circulating biomarkers that might be detected in a simple blood sample to predict patient response to induction chemotherapy. Since exosomes released by tumor cells can drive tumor growth and chemoresistance, we tested the hypothesis that exosomal microRNA (exo-miRNAs) in blood might predict response to induction chemotherapy. The exo-miRNAs expression profile in plasma samples collected from children treated in HR-NBL-1/SIOPEN before and after induction chemotherapy was compared to identify a three exo-miRs signature that could discriminate between poor and good responders. Exo-miRNAs expression also provided a chemoresistance index predicting the good or poor prognosis of HR-NB patients.