Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles
Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles
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DOI：
10.1111/cas.14393
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发表时间：
2020-04-23
期刊：
影响因子：
5.7
通讯作者：
Tahara, Hidetoshi
中科院分区：
文献类型：
--
作者：
Koi, Yumiko;Tsutani, Yasuhiro;Tahara, Hidetoshi
新出现的证据表明，包括微小RNA（miRNAs）及其异构体（isomiRs）以及转移RNA片段（tRFs）在内的小RNA在乳腺癌（BC）中表达不同，并且可以在血液循环中被检测到。循环小RNA和细胞外囊泡（EVs）中的小RNA已成为基于小RNA的癌症检测应用中的理想标志物。在这项研究中，我们首先进行了小RNA测序，以评估乳腺癌患者和无癌个体（对照）血清中循环小RNA的表达。3种小RNA，即miR - 21 - 5p的异构体（3'端添加C）、miR - 23a - 3p和tRF - Lys（TTT）在乳腺癌样本中的表达显著更高，并且在一个独立队列中通过小RNA测序得到了验证。我们使用这3种小RNA构建的模型显示出较高的诊断准确性，受试者工作特征曲线下面积为0.92，并且能够区分0期早期乳腺癌和对照组。为了测试这些小RNA是否由癌细胞释放，我们接下来检测了乳腺癌患者和对照血清中的细胞外囊泡。确定了3种候选小RNA中的2种，并且发现它们在乳腺癌患者的细胞外囊泡中含量丰富。有趣的是，这2种小RNA在乳腺癌细胞系（MCF - 7和MDA - MB - 231）的培养基中也被更大量地检测到。在总血清、血清细胞外囊泡以及来自细胞培养基的细胞外囊泡中观察到的选择性升高的相同趋势可能表明使用患者总血清的这种模型的有效性。这些发现表明小RNA可作为乳腺癌检测的重要生物标志物。
Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3 ' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.