Identification of a MicroRNA Panel for Clear-cell Kidney Cancer
Identification of a MicroRNA Panel for Clear-cell Kidney Cancer
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DOI：
10.1016/j.urology.2009.10.033
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发表时间：
2010-04-01
期刊：
影响因子：
2.1
通讯作者：
Liou, Louis S.
中科院分区：
文献类型：
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作者：
Juan, David;Alexe, Gabriela;Liou, Louis S.
目的确定一组可靠的microRNA信号，利用microRNA表达水平将肿瘤与正常肾脏区分开来。越来越多的证据表明，microRNAs在重要的细胞过程中起着关键作用，其表达模式可以作为癌症组织的诊断生物标志物。方法从患者匹配的标本中选择28例透明细胞型人肾细胞癌(CcRCC)样本，进行高通量、实时定量聚合酶链式反应(RT-PCR)分析microRNA的表达水平。这些数据经过严格的统计分析和层次聚类，产生了一组离散的microRNAs，可以高置信度地将ccRCC与其匹配的正常肾组织样本区分开来。结果发现35个microRNAs可以高置信度地将ccRCC与其匹配的正常肾组织样本区分开来。在这组35个标志性microRNA中，26个在ccRCC中被发现持续下调，9个在ccRCC中持续上调。在我们的研究中，两个microRNAs，即通常在其他癌症中上调的miR-155和miR-21，以及缺氧诱导的miR-210，在ccRCC中也过表达。本研究中发现的下调的microRNAs可能与ccRCC中常见的染色体缺失相关。结论我们的分析是一项综合性的、统计学相关的研究，它确定了ccRCC中表达下调的microRNAs，可作为诊断的分子标记的基础。泌尿外科75：835-841,2010。(C)2010年爱思唯尔公司。
OBJECTIVES To identify a robust panel of microRNA signatures that can classify tumor from normal kidney using microRNA expression levels. Mounting evidence suggests that microRNAs are key players in essential cellular processes and that their expression pattern can serve as diagnostic biomarkers for cancerous tissues.METHODS We selected 28 clear-cell type human renal cell carcinoma (ccRCC), samples from patient-matched specimens to perform high-throughput, quantitative real-time polymerase chain reaction analysis of microRNA expression levels. The data were subjected to rigorous statistical analyses and hierarchical clustering to produce a discrete set of microRNAs that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence.RESULTS Thirty-five microRNAs were found that can robustly distinguish ccRCC from their patient-matched normal kidney tissue samples with high confidence. Among this set of 35 signature microRNAs, 26 were found to be consistently downregulated and 9 consistently upregulated in ccRCC relative to normal kidney samples. Two microRNAs, namely, MiR-155 and miR-21, commonly found to be upregulated in other cancers, and miR-210, induced by hypoxia, were also identified as overexpressed in ccRCC in our study. MicroRNAs identified as downregulated in our study can be correlated to common chromosome deletions in ccRCC.CONCLUSIONS Our analysis is a comprehensive, statistically relevant study that identifies the microRNAs dysregulated in ccRCC, which can serve as the basis of molecular markers for diagnosis. UROLOGY 75: 835-841, 2010. (C) 2010 Elsevier Inc.