Circulating serum miRNAs as potential biomarkers for nephroblastoma
Circulating serum miRNAs as potential biomarkers for nephroblastoma
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DOI：
10.1002/pbc.25481
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发表时间：
2015-08-01
影响因子：
3.2
通讯作者：
Meese, Eckart
中科院分区：
文献类型：
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作者：
Ludwig, Nicole;Nourkami-Tutdibi, Nasenien;Meese, Eckart
肾母细胞瘤是最常见的儿童肾癌。在欧洲，肾母细胞瘤的治疗是术前化疗，没有活检的组织学证实。因此，确认肾母细胞瘤诊断的微创诊断标记是非常有必要的。在我们的研究中，我们的目标是鉴定具有鉴别肾母细胞瘤与对照的诊断潜力的循环mirna。我们用实时荧光定量PCR检测了32例肾母细胞瘤患者和12例对照患者血清中19种mirna的水平。在一个独立的验证集中进一步测试了三种mirna，包括Wilms以外的肾脏肿瘤患者的血清。结果肾母细胞瘤患者血清中14种mirna的丰度明显高于对照组。具有最高诊断潜力的mirna包括miRs-130b-3p、-100-5p和-143-3p， AUC分别为0.94、0.90和0.89。基于这三种mirna的特征将患者与对照组区分开来，准确率为84.58%，灵敏度为76.67%，特异性为92.5%。mir -100-5p和-130b-3p的高表达在一个独立的验证集中被证实。基于miRs-100-5p和-130b-3p的标记区分肾母细胞瘤患者与健康对照者的准确性、敏感性和特异性分别为79.6%、69.2%和90.0%。总之，我们提供了第一个证据，证明血清miR-100-5p和-130b-3p具有作为WT亚型生物标志物的潜力，并且这些miRNA在血清中的表达水平不受血清收集差异的影响。儿科血癌2015；62:1360-1367。(c) 2015 Wiley期刊公司
BackgroundNephroblastoma (or Wilms tumorWT) is the most common childhood kidney cancer. In Europe, nephroblastoma is treated with preoperative chemotherapy without histological confirmation by biopsy. Therefore, minimal-invasive diagnostic markers confirming nephroblastoma diagnosis are highly warranted.ProcedureIn our study, we aim to identify circulating miRNAs with diagnostic potential for differentiating nephroblastoma from controls. We determined the level of 19 miRNAs in serum of 32 patients with nephroblastoma and 12 controls with quantitative real-time PCR. Three miRNAs were further tested in an independent validation set including sera of patients with renal tumors other than Wilms.ResultsIn total, 14 miRNAs showed significantly higher abundance in serum of patients with nephroblastoma than in controls. The miRNAs with highest diagnostic potentials included miRs-130b-3p, -100-5p, and -143-3p with an AUC of 0.94, 0.90, and 0.89, respectively. A signature based on these three miRNAs to differentiated patients from controls with an accuracy of 84.58%, a sensitivity of 76.67%, and a specificity of 92.5%. Higher expression of miRs-100-5p and -130b-3p was confirmed in an independent validation set. The signature based on miRs-100-5p and -130b-3p differentiated patients with nephroblastoma from healthy controls with an accuracy, sensitivity, and specificity of 79.6%, 69.2%, and 90.0%, respectively.ConclusionIn summary, we provide first evidence that serum miR-100-5p and -130b-3p hold potential as biomarker for WT irrespective of the subtype and that expression level of these miRNA in serum is unaffected by differences in serum collection. Pediatr Blood Cancer 2015;62:1360-1367. (c) 2015 Wiley Periodicals, Inc.