Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma.

Circulating miR-378 and miR-451 in serum are potential biomarkers for renal cell carcinoma.
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DOI:
10.1186/1479-5876-10-55
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发表时间:
2012-03-22
影响因子:
7.4
通讯作者:
Slaby O
Slaby O
中科院分区:
医学2区
文献类型:
--
作者:
Redova M;Poprach A;Nekvindova J;Iliev R;Radova L;Lakomy R;Svoboda M;Vyzula R;Slaby O

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目前尚无标准的血清生物标志物用于肾细胞癌(RCC)患者的诊断或早期复发检测。微小RNA(miRNAs)在血清中含量丰富且高度稳定,并且最近被描述为广泛的实体癌中的强有力的循环生物标志物。我们的目的是鉴定能够区分RCC患者和匹配的健康对照血清的miRNA标签,并验证所鉴定的miRNA作为RCC的潜在生物标志物。在该研究的筛选阶段,通过使用TaqMan低密度阵列分析15名RCC患者和12名匹配的健康对照的血清,从而能够通过基于qRT-PCR的方法平行鉴定667个miRNA的表达水平。在验证阶段,通过使用单独的qRT-PCR测定法对90名RCC患者和35名匹配的健康对照的独立组进一步评估鉴定的miRNA并进行统计学评估。我们鉴定了30个在肾细胞癌患者血清和健康对照血清中差异表达的miRNAs,其中19个在肾细胞癌患者血清中表达上调,11个在肾细胞癌患者血清中表达下调。在独立的患者组中进一步评估miR-378、miR-451和miR-150,并且其中两个被成功验证:RCC患者血清中miR-378水平升高(p = 0.0003,AUC = 0.71),miR-451水平降低(p < 0.0001,AUC = 0.77)。miR-378和miR-451的组合使得能够以81%的灵敏度、83%的特异性和AUC = 0.86鉴定RCC血清。血清中的循环miRNA是RCC中有希望的生物标志物。
There is no standard serum biomarker used for diagnosis or early detection of recurrence for renal cell carcinoma (RCC) patients. MicroRNAs (miRNAs) are abundant and highly stable in blood serum, and have been recently described as powerful circulating biomarkers in a wide range of solid cancers. Our aim was to identify miRNA signature that can distinguish the blood serum of RCC patients and matched healthy controls and validate identified miRNAs as potential biomarkers for RCC. In the screening phase of the study, blood serum of 15 RCC patients and 12 matched healthy controls were analyzed by use of the TaqMan Low-Density Arrays enabling parallel identification of expression levels of 667 miRNAs through qRT-PCR-based approach. In the validation phase, identified miRNAs were further evaluated on the independent group of 90 RCC patients and 35 matched healthy controls by use of individual qRT-PCR assays and statistically evaluated. We identified 30 miRNAs differentially expressed between serum of RCC patients and healthy controls: 19 miRNAs were up-regulated and 11 miRNAs were down-regulated in RCC patients. MiR-378, miR-451 and miR-150 were further evaluated in the independent group of patients, and two of them were successfully validated: levels of miR-378 were increased (p = 0.0003, AUC = 0.71), miR-451 levels were decreased (p < 0.0001, AUC = 0.77) in serum of RCC patients. Combination of miR-378 and miR-451 enable identification of RCC serum with the sensitivity of 81%, specificity 83% and AUC = 0.86. Circulating miRNAs in serum are promising biomarkers in RCC.
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