Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls
Serum microRNA profiling and breast cancer risk: the use of miR-484/191 as endogenous controls
复制标题
血清 microRNA 分析和乳腺癌风险：使用 miR-484/191 作为内源性对照
DOI：
10.1093/carcin/bgs030
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发表时间：
2012-04-01
期刊：
影响因子：
4.7
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
--
作者：
Hu, Zhibin;Dong, Jing;Shen, Hongbing
已有研究表明，血浆/血清中含有丰富的稳定的microRNAs(MiRNAs)，它们可以被检测到，并且具有潜在的疾病特异性。然而，缺乏合适的血清miRNA检测的内源性对照，限制了这类生物标志物的广泛使用和实验室间的结果比较。我们首先通过测试10个不同癌症性状的混合样本(使用Solexa测序和TaqMan低密度阵列)和50个单独样本(使用定量逆转录-聚合酶链式反应)来系统地筛选内源调控miRNAs(ECM)。然后，我们基于两阶段病例对照分析，评估了血清miRNAs作为乳腺癌风险预测的潜在生物标记物的作用，包括48名乳腺癌患者和48名发现阶段的对照，76名乳腺癌患者和76名对照进行验证。我们鉴定了两个候选ECM(miRNA-191和miRNA-484)。经两种ECM归一化后，我们发现四个miRNAs(miR-16、miR-25、miR-222和miR-324-3p)在乳腺癌患者和对照组中持续差异表达。在发现阶段，四-miRNA签名的接收者操作特征曲线下面积为0.954(灵敏度=0.917，特异度=0.896)，在验证阶段，接收器工作特征曲线下面积为0.928(灵敏度=0.921，特异度=0.934)。综上所述，血清中的4-miRNA标志可作为乳腺癌的非侵入性预测生物标志物。此外，我们建议将miRNA-484和miRNA-191结合起来作为血清miRNA检测的内源性对照，至少对大多数常见的癌症是如此。
It has been demonstrated that there are abundant stable microRNAs (miRNAs) in plasma/serum, which can be detected and are potentially disease specific. However, the lack of suitable endogenous controls for serum miRNA detection is the restriction for the widely usage of this kind of biomarkers and for the between-laboratory comparison of the findings. We first systematically screened for endogenous control miRNAs (ECMs) by testing 10 pooling samples (using both Solexa sequencing and TaqMan low density array) and 50 individual samples (using quantitative reverse transcription-PCR) of different cancer traits and healthy controls. Then we assessed serum miRNAs used as potential biomarkers for breast cancer risk prediction based on a two-stage case-control analysis, including 48 breast cancer patients and 48 controls for the discovery stage and 76 breast cancer patients and 76 controls for validation. We identified two candidate ECMs (miRNA-191 and miRNA-484). Normalized by the two ECMs, we found four miRNAs (miR-16, miR-25, miR-222 and miR-324-3p) that were consistently differentially expressed between breast cancer cases and controls. The area under the receiver operating characteristic curve is 0.954 for the four-miRNA signature in the discovery stage (sensitivity = 0.917 and specificity = 0.896) and 0.928 in the validation stage (sensitivity = 0.921 and specificity = 0.934). In conclusion, the four-miRNA signature from serum may serve as a non-invasive prediction biomarker for breast cancer. Furthermore, we proposed the combination of miRNA-484 and miRNA-191 as endogenous control for serum miRNA detection, at least for most common cancers.