Circulating microRNAs from the miR-106a-363 cluster on chromosome X as novel diagnostic biomarkers for breast cancer.
Circulating microRNAs from the miR-106a-363 cluster on chromosome X as novel diagnostic biomarkers for breast cancer.
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X 染色体上 miR-106a-363 簇的循环 microRNA 作为乳腺癌的新型诊断生物标志物
DOI：
10.1007/s10549-018-4757-3
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发表时间：
2018-07
影响因子：
3.8
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Li M;Zhou Y;Xia T;Zhou X;Huang Z;Zhang H;Zhu W;Ding Q;Wang S
临床上迫切需要一种新的、具有高敏感性和特异性的非侵入性乳腺癌诊断标志物。本研究的目的是探索是否可以在BC患者的循环中检测到来自miR-106 a-363簇的miRNA，以及这些miRNA是否可以作为潜在的诊断生物标志物。通过一项三阶段研究，使用qRT-PCR在400份血浆样品（来自200名BC患者和200名健康对照（HC））和406份血清样品（来自204名BC患者和202名HC）中评估了来自miR-106 a-363簇的12种miRNA的表达。在组织（32对乳腺组织）、血浆外泌体（来自32名BC患者和32名HC）和血清外泌体（来自32名BC患者和32名HC）中进一步检查鉴定的miRNA。在BC中鉴定并验证了四种血浆miRNA（miR-106 a-3 p、miR-106 a-5 p、miR-20 b-5 p和miR-92 a-2- 5 p）和四种血清miRNA（miR-106 a-5 p、miR-19 b-3 p、miR-20 b-5 p和miR-92 a-3 p）的上调水平。构建血浆4-miRNA组和血清4-miRNA组以区分BC患者与HC。在培训、检测和外部验证阶段，血浆样本组的受试者工作特征曲线下面积分别为0.880、0.902和0.858，血清样本组的受试者工作特征曲线下面积分别为0.910、0.974和0.949。两种重叠的miRNA（miR-106 a-5 p和miR-20 b-5 p）在BC组织中一致地上调。除血浆来源的外泌体miR-20 b-5 p的表达外，外泌体miRNA的表达模式在血浆和血清之间是一致的，表明外泌体miRNA作为生物标志物的潜在用途。我们从miR-106 a-363簇中鉴定了四种血浆miRNA和四种血清miRNA，作为诊断BC的有希望的新生物标志物。本文的在线版本（10.1007/s10549-018-4757-3）包含补充材料，可供授权用户使用。
Novel noninvasive biomarkers with high sensitivity and specificity for the diagnosis of breast cancer (BC) are urgently needed in clinics. The aim of this study was to explore whether miRNAs from the miR-106a–363 cluster can be detected in the circulation of BC patients and whether these miRNAs can serve as potential diagnostic biomarkers. The expression of 12 miRNAs from the miR-106a–363 cluster was evaluated using qRT-PCR in 400 plasma samples (from 200 BC patients and 200 healthy controls (HCs)) and 406 serum samples (from 204 BC patients and 202 HCs) via a three-phase study. The identified miRNAs were further examined in tissues (32 paired breast tissues), plasma exosomes (from 32 BC patients and 32 HCs), and serum exosomes (from 32 BC patients and 32 HCs). Upregulated levels of four plasma miRNAs (miR-106a-3p, miR-106a-5p, miR-20b-5p, and miR-92a-2-5p) and four serum miRNAs (miR-106a-5p, miR-19b-3p, miR-20b-5p, and miR-92a-3p) were identified and validated in BC. A plasma 4-miRNA panel and a serum 4-miRNA panel were constructed to discriminate BC patients from HCs. The areas under the receiver-operating characteristic curves of the plasma panel were 0.880, 0.902, and 0.858, and those of the serum panel were 0.910, 0.974, and 0.949 for the training, testing, and external validation phases, respectively. Two overlapping miRNAs (miR-106a-5p and miR-20b-5p) were consistently upregulated in BC tissues. Except for the expression of the plasma-derived exosomal miR-20b-5p, the expression patterns of exosomal miRNAs were concordant between plasma and serum, indicating the potential use of exosomal miRNAs as biomarkers. We identified four plasma miRNAs and four serum miRNAs from the miR-106a–363 cluster as promising novel biomarkers for the diagnosis of BC. The online version of this article (10.1007/s10549-018-4757-3) contains supplementary material, which is available to authorized users.
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