Yang He, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China, Tel.: +86 512 6778 1379, Fax: +86 512 6510 1708, E-mail:
Thromb Haemost. 2017 Jun 28;117(7):1420-1431. doi: 10.1160/TH-16-06-0481. Epub 2017 Apr 20.
Altered microRNA (miRNA) expression has been reported in patients with immune thrombocytopenic purpura (ITP). However, the detailed expression profiling of cell-free circulating miRNAs in ITP patients has not been fully investigated. In this study, we aimed to examine plasma miRNAs in ITP patients and evaluate their diagnostic values. Plasma samples from 74 ITP patients and 58 healthy controls were obtained and allocated into discovery, validation, and therapy-response sets. Initial screen with a miRNA microarray assay identified 23 miRNAs with different levels between ITP patients and healthy controls (>1.5-fold changes; p<0.01). Subsequent quantitative real-time PCR confirmed eight up-regulated miRNAs (miR-320c, miR-642b-3p, miR-1275, miR-3141, miR-4270, miR-4499, miR-4739 and miR-6126) and three down-regulated miRNAs (miR-144-3p, miR-1281 and miR-3162-3p) in ITP patients. The levels of these circulating miRNAs varied, depending on ITP subtypes, i.e. newly-diagnosed, persistent and chronic ITP, and between treatment responders and non-responders. In receiver operator characteristic analysis, 10 miRNAs had positive diagnostic values (p<0.05) when tested individually. The diagnostic value improved when the miRNAs were analysed as a panel or together with the analysis of anti-platelet autoantibodies. Plasma miR-3162-3p levels were also found to positively correlate with platelet counts in ITP patients (r=0.338, p=0.01). Our results indicate that plasma miRNA profiles are altered in ITP patients and that the differentially expressed miRNAs may be used as biomarkers to improve the diagnosis of ITP.
已有研究报道,免疫性血小板减少症(immune thrombocytopenic purpura,ITP)患者的微小 RNA(microRNA,miRNA)表达谱发生改变。然而,ITP 患者循环游离细胞 miRNA 的详细表达谱尚未得到充分研究。本研究旨在探讨 ITP 患者血浆 miRNA 的表达情况,并评估其诊断价值。收集 74 例 ITP 患者和 58 例健康对照者的血浆样本,分为发现、验证和治疗反应组。采用 miRNA 微阵列分析初始筛选发现,ITP 患者与健康对照者间有 23 个 miRNA 的表达水平存在差异(差异倍数>1.5 倍;p<0.01)。随后通过实时定量 PCR 验证了 8 个上调的 miRNA(miR-320c、miR-642b-3p、miR-1275、miR-3141、miR-4270、miR-4499、miR-4739 和 miR-6126)和 3 个下调的 miRNA(miR-144-3p、miR-1281 和 miR-3162-3p)在 ITP 患者中表达上调。这些循环 miRNA 的水平因 ITP 亚型(新发、持续和慢性 ITP)和治疗反应者与非反应者而有所不同。在受试者工作特征分析中,当单独检测时,10 个 miRNA 具有阳性诊断价值(p<0.05)。当分析这些 miRNA 作为一个 panel 或与抗血小板自身抗体分析相结合时,诊断价值有所提高。在 ITP 患者中,还发现血浆 miR-3162-3p 水平与血小板计数呈正相关(r=0.338,p=0.01)。本研究结果表明,ITP 患者的血浆 miRNA 谱发生改变,差异表达的 miRNA 可能作为生物标志物用于提高 ITP 的诊断。