循环 microRNA 标志物在神经母细胞瘤患者转移疾病中的应用。
Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients.
机构信息
Center for Medical Genetics, Department of Biomolecular Medicine, and.
Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.
出版信息
JCI Insight. 2018 Dec 6;3(23):97021. doi: 10.1172/jci.insight.97021.
In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.
在这项研究中，评估了来自诊断性神经母细胞瘤血清的循环 miRNA 组，以鉴定具有监测转移性疾病潜力的非侵入性生物标志物。在确定了循环神经母细胞瘤 miRNA 组后，在两个独立的 131 名和 54 名患者队列中筛选了 743 个 miRNA。在一个用于检测肿瘤分期、MYCN 状态、诊断时年龄和总生存期的模型中评估血清 miRNA 变异，结果显示肿瘤分期是影响神经母细胞瘤血清中 miRNA 丰度的最显著因素。对转移性和局限性疾病患者进行差异丰度分析，在两个患者队列中均发现 9 个 miRNA 与转移性 4 期疾病强烈相关。在携带人神经母细胞瘤肿瘤的异种移植小鼠的血清中也观察到这些 miRNA 水平的升高。此外，鼠血清 miRNA 水平与肿瘤体积强烈相关。这些发现通过对转移性神经母细胞瘤患者的纵向血清样本进行验证，其中 9 个 miRNA 与疾病负担和治疗反应相关。
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