Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma.
Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma.
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低血清 miR-19a 表达作为多发性骨髓瘤的新型不良预后指标
DOI：
10.1002/ijc.29199
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发表时间：
2015-04-15
影响因子：
6.4
通讯作者：
Qiu, Lugui
中科院分区：
文献类型：
--
作者：
Hao, Mu;Zang, Meirong;Wendlandt, Erik;Xu, Yan;An, Gang;Gong, Dasen;Li, Fei;Qi, Fang;Zhang, Yanru;Yang, Ye;Zhan, Fenghuang;Qiu, Lugui
多发性骨髓瘤（MM）是第二常见的恶性血液病，其特征是浆细胞的克隆性扩增。尽管不断取得进展，新的生物标志物需要MM的诊断和预后。在这项研究中，我们的特点是诊断和预后潜力的循环miRNA在MM。血清miRNA水平进行了分析，在108个新诊断的症状MM患者和56个健康供体（HD）。我们的分析在新诊断的MM患者中鉴定了95种失调的miRNA。在95种失调的miRNA中，通过RT-qPCR证实了miR-19 a、miR-92 a、miR-214- 3 p、miR-135 b-5 p、miR-4254、miR-3658和miR-33 b的失调。受试者操作特征分析显示，miR-19 a和miR-4254的组合可以区分MM和HD，灵敏度为91.7%，特异性为90.5%。miR-19 a表达降低与国际分期系统进展、del（13 q14）和1 q21扩增呈正相关。此外，miR-19 a的下调导致无进展生存期和总生存期显著降低。我们的分析表明，miR-19 a表达的不良预后相关性与MM的遗传异常无关。多变量分析显示，miR-19 a是PFS和OS缩短的重要预测因子。有趣的是，尽管miR-19 a水平预示着不良预后，但与miR-19 a水平高的患者相比，miR-19 a水平低的患者对硼替佐米的反应有所改善。miR-19 a下调的患者在硼替佐米治疗后生存期显著延长。这些数据表明，血清microRNA的表达模式在MM中发生改变，miR-19 a水平是识别高危MM的有价值的预后标志物。
Multiple myeloma (MM) is the second most common hematologic malignancy characterized by the clonal expansion of plasma cells. Despite continuing advances, novel biomarkers are needed for diagnosis and prognosis of MM. In this study we characterized the diagnostic and prognostic potential of circulating miRNAs in MM. Serum miRNA levels were analyzed in 108 newly diagnosed symptomatic MM patients and 56 healthy donors (HD). Our analysis identified ninety-five dysregulated miRNAs in newly diagnosed MM patients. Of the ninety-five dysregulated miRNAs, dysregulation of miR-19a, miR-92a, miR-214-3p, miR-135b-5p, miR-4254, miR-3658 and miR-33b were confirmed by RT-qPCR. Receiver operating characteristic analysis revealed that a combination of miR-19a and miR-4254 can distinguish MM from HD with a sensitivity of 91.7% and specificity of 90.5%. Decreased expression of miR-19a was positively correlated with international staging system advancement, del(13q14) and 1q21 amplification. Furthermore, down-regulation of miR-19a resulted in significantly decreased progression free and overall survival. Our analysis indicated that the poor prognostic correlation of miR-19a expression was independent of genetic abnormalities in MM. Multivariate analysis revealed that miR-19a was a significant predictor of shortened PFS and OS. Interestingly, although miR-19a levels portend a poor prognosis, patients with low miR-19a levels had an improved response to bortezomib compared to patients with high miR-19a profile. Patients with down-regulated miR-19a experienced a significantly extended survival upon bortezomib based therapy. These data demonstrate that the expression patterns of serum microRNAs are altered in MM and miR-19a levels are a valuable prognostic marker to identify high-risk MM.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
3.7
作者：
Eguchi T;Watanabe K;Hara ES;Ono M;Kuboki T;Calderwood SK
通讯作者：
Calderwood SK
影响因子：
4.5
作者：
Grillari, Johannes;Hackl, Matthias;Grillari-Voglauer, Regina
通讯作者：
Grillari-Voglauer, Regina
染色体 1q21 增加导致用硼替佐米治疗的多发性骨髓瘤预后较差，但拷贝数变异和所涉及浆细胞的百分比没有额外的预后价值
影响因子：
10.1
作者：
An, Gang;Xu, Yan;Qiu, Lugui
通讯作者：
Qiu, Lugui
影响因子：
8.4
作者：
Koeberle, Verena;Kronenberger, Bernd;Waidmann, Oliver
通讯作者：
Waidmann, Oliver