MicroRNA-15a/16-1 cluster located at chromosome 13q14 is down-regulated but displays different expression pattern and prognostic significance in multiple myeloma.
MicroRNA-15a/16-1 cluster located at chromosome 13q14 is down-regulated but displays different expression pattern and prognostic significance in multiple myeloma.
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位于染色体 13q14 的 MicroRNA-15a/16-1 簇下调，但在多发性骨髓瘤中表现出不同的表达模式和预后意义
DOI：
10.18632/oncotarget.5681
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发表时间：
2015-11-10
期刊：
影响因子：
--
通讯作者：
Qiu L
中科院分区：
文献类型：
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作者：
Li F;Xu Y;Deng S;Li Z;Zou D;Yi S;Sui W;Hao M;Qiu L
位于染色体13q14的MiRNA-15a/16-1簇已被证实在多发性骨髓瘤（multiple myeloma， MM）中调控与细胞增殖、凋亡和耐药相关的关键基因。然而，关于它们在MM患者中的表达模式和预后价值知之甚少。在这项研究中，我们通过实时荧光定量PCR分析了miR-15a/16-1在117名MM患者（90名新诊断患者，11名复发患者和16名缓解患者）和19名健康供体（hd）中的表达水平。我们的研究结果表明，与hd相比，新诊断的MM患者中miR-15a和16-1的表达水平下调（P = 0.025; P < 0.001），且与del无关（13q14）。miR-15a下调与疾病进展和不良预后显著相关，而miR-16-1似乎是区分MM和hd的良好诊断标志物，曲线下面积（AUC）为0.864，敏感性为100%，特异性为73%。此外，miR-15a < 2.35（低表达组）患者的PFS （P < 0.001）和OS （P < 0.001）均显著缩短。在调整已建立的预后变量包括del（13q）、del（17p）、amp（1q21）和高危遗传异常后，miR-15a低表达（<2.35）仍然是PFS （P = 0.008）和OS （P = 0.038）的有力独立预测因子。此外，miR-15a结合高β2-MG和高危遗传异常可以进一步识别高危亚群。因此，我们的数据表明miR-15a/16-1在MM患者中的表达模式是不同的，miR-15a似乎与疾病进展和预后有关，而miR-16-1则是一个有价值的诊断标志物。
MiRNA-15a/16-1 cluster located at chromosome 13q14 has been confirmed to regulate critical genes associated with cell proliferation, apoptosis and drug resistance in multiple myeloma (MM). However, little is known about their expression pattern and prognostic value in MM patients. In this study, we have analyzed the expression levels of miR-15a/16-1 in 117 MM patients (90 newly diagnosed, 11 relapsed and 16 remission patients) and 19 health donors (HDs) by quantitative real-time PCR. Our results indicated that the expression levels of miR-15a and 16-1 were down-regulated in newly diagnosed MM patients as compared to HDs (P = 0.025; P < 0.001) and independent of del(13q14). Downregulation of miR-15a was significantly associated with disease progression and poor prognosis while miR-16-1 seemed to be a good diagnostic marker to distinguish MM from HDs with area under the curve (AUC) of 0.864, sensitivity of 100% and specificity of 73%. Furthermore, patients with miR-15a < 2.35 (low expression group) had significantly shorter PFS (P < 0.001) and OS (P < 0.001). After adjustment of the established prognostic variables including del(13q), del(17p), amp(1q21) and high risk genetic abnormality, low miR-15a expression (<2.35) was still a powerful independent predictor for PFS (P = 0.008) and OS (P = 0.038). In addition, miR-15a combined with high β2-MG and high risk genetic abnormality can further identify the high-risk subpopulations. Therefore, our data suggest that the expression patterns of miR-15a/16-1 are different in MM patients, and miR-15a seems to be linked with disease progression and prognosis while miR-16-1 acts as a valuable diagnostic marker.