Department of Pathology, Boston University, Boston, Massachusetts 02118, USA.
Urology. 2010 Apr;75(4):835-41. doi: 10.1016/j.urology.2009.10.033. Epub 2009 Dec 29.
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.
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.
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.
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.
通过微 RNA 表达水平,确定一组可用于区分肿瘤与正常肾脏的稳健 miRNA 特征。越来越多的证据表明,miRNAs 是重要细胞过程的关键参与者,其表达模式可以作为癌症组织的诊断生物标志物。
我们选择了 28 例透明细胞型人肾细胞癌(ccRCC)患者配对标本,进行 miRNA 表达水平的高通量、定量实时聚合酶链反应分析。对数据进行严格的统计分析和层次聚类,产生一组离散的 miRNA,能够以高置信度从其患者配对的正常肾脏组织样本中稳健地区分 ccRCC。
发现 35 个 miRNA 可以高置信度地从其患者配对的正常肾脏组织样本中稳健地区分 ccRCC。在这组 35 个特征 miRNA 中,有 26 个 miRNA 在 ccRCC 中一致下调,9 个 miRNA 一致上调。在我们的研究中,两个 miRNA(miR-155 和 miR-21)通常在其他癌症中上调,miR-210 由缺氧诱导,也被鉴定为在 ccRCC 中过表达。在我们的研究中下调的 miRNA 可以与 ccRCC 中常见的染色体缺失相关。
我们的分析是一项全面的、具有统计学意义的研究,确定了在 ccRCC 中失调的 miRNA,它们可以作为诊断分子标志物的基础。