University Clinic of Urology, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
Int J Cancer. 2012 Feb 1;130(3):611-21. doi: 10.1002/ijc.26064. Epub 2011 May 9.
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real-time PCR and the identity of miRNA expressing cells was determined by miRNA in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both techniques. The differential expression of miRNAs miR-375, miR-143 and miR-145 was validated by quantitative PCR. MiRNA in situ hybridization revealed that the differential expression is cancer-cell associated. A combination of three miRNAs correctly classified tissue samples with an accuracy of 77.6% with an area under the receiver-operator characteristic curve of 0.810. Our data extend the knowledge about the deregulation of miRNAs in prostate cancer. The differential expression of several miRNAs is highly consistent using independent cohorts of tumor samples, different tissue preservation methods and different experimental methods. Our results indicate that combinations of miRNAs are promising biomarkers for the diagnosis of prostate cancer.
微小 RNA(miRNA)是一种通过转录后抑制蛋白质合成来调节基因表达的小 RNA 分子。它们在肿瘤发生中起着至关重要的作用。为了描述 miRNA 在前列腺癌(一种主要的癌症致死原因)中的诊断潜力,我们进行了 miRNA 表达谱筛选。我们使用商业上可用的微阵列从 20 个癌症样本的队列中建立 miRNA 表达谱。通过定量实时 PCR 分析选定 miRNA 的表达,并通过 miRNA 原位杂交确定表达 miRNA 的细胞的身份。我们确定了 25 个在癌症样本中表现出显著差异表达的 miRNA。与之前通过 cDNA 文库的深度测序发表的 miRNA 数据进行比较,两种技术鉴定的 miRNA 具有 47%的一致性。miR-375、miR-143 和 miR-145 的 miRNA 差异表达通过定量 PCR 得到验证。miRNA 原位杂交显示,这种差异表达与癌细胞有关。三种 miRNA 的组合以 77.6%的准确率正确分类组织样本,接收器操作特性曲线下的面积为 0.810。我们的数据扩展了 miRNA 在前列腺癌中失调的知识。使用独立的肿瘤样本队列、不同的组织保存方法和不同的实验方法,几种 miRNA 的差异表达高度一致。我们的结果表明,miRNA 组合是前列腺癌诊断的有前途的生物标志物。