Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling
Identification of microRNA biomarkers in the blood of breast cancer patients based on microRNA profiling
复制标题
基于 microRNA 分析鉴定乳腺癌患者血液中的 microRNA 生物标志物。
DOI：
10.1016/j.gene.2017.03.038
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发表时间：
2017-07-01
期刊：
影响因子：
3.5
通讯作者：
Ma, Rong
中科院分区：
文献类型：
--
作者：
Zhang, Kai;Wang, Ya-Wen;Ma, Rong
越来越多的证据表明，人类循环microRNAs （miRNAs）可以作为各种癌症的诊断和预后生物标志物。我们的目的是在miRNA分析的基础上探索乳腺癌患者血液中的新型miRNA生物标志物。采用miRCURY (TM) LNA Array检测乳腺癌患者（n = 6）和健康对照组（n = 6）全血中差异改变的mirna。采用定量逆转录聚合酶链反应（qRT-PCR）对15例乳腺癌患者和13例年龄匹配的健康对照者的全血标本中候选mirna的水平进行了定量分析。miRWalk数据库用于预测miRNA靶标，DAVID工具用于识别重要的富集途径。通过微阵列共鉴定出171个差异表达的mirna，其中169个在乳腺癌中表达上调，2个表达下调。通过qRT-PCR确认了5个上调的miRNAs （miR-30b-5p、miR-96-5p、miR-182-5p、miR-374b-5p和miR-942-5p）。miR-30b-5p、miR-96-5p、miR-182-5p、miR-374b-5p、miR-942-5p的受试者工作特征曲线下面积分别为0.9333、0.7692、0.7590、0.8256、0.8128。重要的是，即使在非常早期的乳腺癌患者中也观察到这五种mirna的上调。预计共855个基因被这5种miRNAs靶向，其中1个切割结构域家族成员2基因（ONECUT2）是这5种miRNAs的共同靶点。对公开数据的分析显示，这些失调的mirna和靶基因与乳腺癌患者的生存有关。此外，这5种mirna在多种癌症相关通路中显著富集，包括“microrna in cancer”、“pathways in cancer”、“FoxO signaling pathway”、“Ras signaling pathway”、“Rap1 signaling pathway”、“MAPK signaling pathway”和“PI3K-Akt signaling pathway”。我们的数据支持这5种鉴定的mirna作为检测乳腺癌的新型生物标志物的潜力，并表明它们可能参与乳腺癌的发生和进展。(C) 2017 Elsevier B.V.版权所有
Accumulating evidence indicates that human circulating microRNAs (miRNAs) could serve as diagnostic and prognostic biomarkers in various cancers. We aimed to explore novel miRNA biomarkers in the blood of breast cancer patients based on miRNA profiling. A miRCURY (TM) LNA Array was used to identify differentially altered miRNAs in the whole blood of breast cancer patients (n = 6) and healthy controls (n = 6). Levels of candidate miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in whole blood specimens of 15 breast cancer patients and 13 age-matched healthy control individuals. The miRWalk database was used to predict miRNA targets and the DAVID tool was used to identify significant enrichment pathways. A total of 171 differentially expressed miRNAs were identified by microarray, including 169 upregulated and 2 downregulated miRNAs in breast cancer. Five upregulated miRNAs (miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p) were confirmed by qRT-PCR. The areas under the receiver operating characteristic curve of miR-30b-5p, miR-96-5p, miR-182-5p, miR-374b-5p, and miR-942-5p were 0.9333, 0.7692, 0.7590, 0.8256, and 0.8128, respectively. Importantly, upregulation of these five miRNAs was observed even in patients with very early-stage breast cancer. A total of 855 genes were predicted to be targeted by the five miRNAs, and the one cut domain family member 2 gene (ONECUT2) was a shared target of the five miRNAs. Analysis of publicly available data revealed that these dysregulated miRNAs and the target genes were associated with the survival of breast cancer patients. Furthermore, the five miRNAs were significantly enriched in numerous cancer-related pathways, including "MicroRNAs in cancer", "Pathways in cancer", "FoxO signaling pathway", "Ras signaling pathway", "Rap1 signaling pathway", "MAPK signaling pathway", and "PI3K-Akt signaling pathway". Our data support the potential of the five identified miRNAs as novel biomarkers for the detection of breast cancer, and indicate that they may be involved in breast cancer development and progression. (C) 2017 Elsevier B.V. All rights reserved.