Department of Breast Surgery, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
Department of Nursing, Yixing People's Hospital, Jiangsu, People's Republic of China.
Breast Cancer Res Treat. 2018 Jul;170(2):257-270. doi: 10.1007/s10549-018-4757-3. Epub 2018 Mar 20.
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.
临床上急需具有高灵敏度和特异性的新型非侵入性生物标志物来诊断乳腺癌（BC）。本研究旨在探讨 miR-106a-363 簇中的 miRNAs 是否可以在 BC 患者的循环中检测到，以及这些 miRNAs 是否可以作为潜在的诊断生物标志物。
通过三阶段研究，使用 qRT-PCR 评估了 400 个血浆样本（来自 200 名 BC 患者和 200 名健康对照（HC））和 406 个血清样本（来自 204 名 BC 患者和 202 名 HCs）中 12 个来自 miR-106a-363 簇的 miRNA 的表达。通过进一步检测组织（32 对乳腺组织）、血浆外泌体（来自 32 名 BC 患者和 32 名 HCs）和血清外泌体（来自 32 名 BC 患者和 32 名 HCs）来验证鉴定出的 miRNA。
发现并验证了四种血浆 miRNA（miR-106a-3p、miR-106a-5p、miR-20b-5p 和 miR-92a-2-5p）和四种血清 miRNA（miR-106a-5p、miR-19b-3p、miR-20b-5p 和 miR-92a-3p）在 BC 中上调。构建了血浆 4 miRNA 面板和血清 4 miRNA 面板以区分 BC 患者和 HCs。血浆面板的训练、测试和外部验证阶段的受试者工作特征曲线下面积分别为 0.880、0.902 和 0.858，血清面板的分别为 0.910、0.974 和 0.949。两种重叠的 miRNA（miR-106a-5p 和 miR-20b-5p）在 BC 组织中均上调。除了血浆来源的外泌体 miR-20b-5p 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-106a-363 簇中鉴定出四种血浆 miRNA 和四种血清 miRNA，作为 BC 诊断的有前途的新型生物标志物。
