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血浆中七种 miRNA 特征组成的 panel 作为结直肠癌诊断的潜在生物标志物。

A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis.

机构信息

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China; Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215006, PR China.

出版信息

Gene. 2019 Mar 1;687:246-254. doi: 10.1016/j.gene.2018.11.055. Epub 2018 Nov 17.

Abstract

Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection.

摘要

结直肠癌(CRC)是全球最常见的癌症之一。患者血浆中 microRNA(miRNA)的差异表达谱有可能作为一种诊断生物标志物。我们进行了四阶段研究,以确定潜在的 CRC 检测血浆 miRNA。在初始筛选阶段,使用 Exiqon 面板(miRCURY-Ready-to-Use-PCR-Human-panel-I+II-V1.M),包括 3 个 CRC 池和 1 个正常对照(NC)池,获取 miRNA 谱。在训练阶段(30 个 CRC 与 30 个 NC)和测试阶段(79 个 CRC 与 76 个 NC),使用定量实时聚合酶链反应(qRT-PCR)进行候选 miRNA 谱分析。然后在外部验证阶段(30 个 CRC 与 26 个 NC)验证鉴定的 miRNA。在组织样本(24 对)和血浆外泌体(18 个 CRC 与 18 个 NC)中评估鉴定的 miRNA 的表达水平。构建接收者操作特征(ROC)曲线以评估诊断准确性。与 NC 相比,CRC 中七种 miRNA(miR-103a-3p、miR-127-3p、miR-151a-5p、miR-17-5p、miR-181a-5p、miR-18a-5p 和 miR-18b-5p)的表达明显升高。该七 miRNA 特征的 ROC 曲线下面积在训练、测试和外部验证阶段分别为 0.762、0.824 和 0.895。此外,miR-103a-3p、miR-127-3p、miR-17-5p 和 miR-18a-5p 在 CRC 组织中发现明显上调;而 miR-17-5p、miR-181a-5p、miR-18a-5p 和 miR-18b-5p 在 CRC 血浆外泌体中显著升高。总之,我们建立了一种外周血浆 CRC 检测的七 miRNA 特征。

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