Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma.
Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma.
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DOI：
10.1016/j.ygyno.2014.01.029
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发表时间：
2014-03
影响因子：
4.7
通讯作者：
Ozora Tsukamoto;K. Miura;H. Mishima;S. Abe;M. Kaneuchi;A. Higashijima;S. Miura;A. Kinoshita;K. Y
中科院分区：
文献类型：
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作者：
Ozora Tsukamoto;K. Miura;H. Mishima;S. Abe;M. Kaneuchi;A. Higashijima;S. Miura;A. Kinoshita;K. Y
本研究旨在鉴定组织和血浆中的一组子宫内膜样癌EEC相关的microRNAs（miRNAs），并评估其临床意义。MethodsA组EEC相关的miRNAs在组织和血浆中通过下一代测序（NGS）鉴定，这可以使全球miRNA.ResultsNGS鉴定11个候选EEC相关的miRNAs。定量逆转录酶PCR在组织中鉴定出8种与EC相关的miRNA（上调的：miR-499、miR-135 b、miR-205;下调的：miR-10 b、miR-195、miR-30 a-5 p、miR-30 a-3 p和miR-21）。hsa-miR-499在国际妇产科联合会（FIGO）IA期和1级组织中的表达显著低于其他组织（FIGO IB期或更晚期，以及2级或3级）。通过受试者工作特征（ROC）曲线分析，与单个EEC相关miRNA相比，两个miRNA标签（miR 135 b/miR 195和miR 135 b/miR 30 a-3 p）可以区分EEC和正常子宫内膜组织样品，产生0.9835的高曲线下面积（AUC）[95%置信区间（CI）：0.9677-1.0]和0.9898（95% CI：0.9677-1.0）。作为EEC的可能的非侵入性标志物，在血浆中鉴定了四种EEC相关的miRNA（水平升高：miR-135 b和miR-205，水平降低：miR-30 a-3 p和miR-21）。子宫切除术后，血浆中三种EEC相关miRNA（miR-135 b、miR-205和miR-30 a-3 p）的循环水平显著降低。ROC曲线分析显示，血浆中miR-135 b和miR-205水平的AUC分别为0.9722（95%CI：0.913-1.0）和1.0（95%CI：1.0-1.0）。
ObjectiveThis study aimed to identify a set of endometrioid endometrial carcinoma EEC-associated microRNAs (miRNAs) in tissue and plasma, and evaluate their clinical significance.MethodsA set of EEC-associated miRNAs in tissue and plasma was identified by next-generation sequencing (NGS), which could enable in-depth characterization of the global repertoire of miRNAs.ResultsNGS identified 11 candidate EEC-associated miRNAs. Quantitative reverse-transcriptase PCR identified 8 EEC-associated miRNAs in tissue (upregulated: miR-499, miR-135b, miR-205, downregulated: miR-10b, miR-195, miR-30a-5p, miR-30a-3p and miR-21). Expression of hsa-miR-499 in International Federation of Gynecology and Obstetrics (FIGO) Stage IA and Grade 1 tissues was significantly lower than in others (FIGO Stage IB or more advanced, and Grade 2 or 3). By receiver operating characteristic (ROC) curve analysis, compared with single EEC-associated miRNA, two miRNA signatures (miR135b/miR195 and miR135b/miR30a-3p) could distinguish between EEC and normal endometrial tissue samples yielding a high area under the curve (AUC) of 0.9835 [95% confidence interval (CI): 0.9677–1.0], and 0.9898 (95% CI: 0.9677–1.0), respectively. As possible non-invasive markers for EEC, four EEC-associated miRNAs (increased level: miR-135b and miR-205, decreased-level: miR-30a-3p and miR-21) in plasma were identified. Circulating levels of three EEC-associated miRNAs (miR-135b, miR-205 and miR-30a-3p) in plasma were significantly decreased after hysterectomy. ROC curves analysis revealed that miR-135b and miR-205 levels in plasma yielded AUCs of 0.9722 (95% CI: 0.913–1.0) and 1.0 (95% CI: 1.0–1.0), respectively.ConclusionMeasurement of tissue and plasma EEC-associated miRNAs may be useful for early detection, diagnostic, and follow-up tests for EEC.