Downregulated miR-33b is a novel predictor associated with disease progression and poor prognosis in multiple myeloma
Downregulated miR-33b is a novel predictor associated with disease progression and poor prognosis in multiple myeloma
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下调的 miR-33b 是与多发性骨髓瘤疾病进展和不良预后相关的新型预测因子
DOI：
10.1016/j.leukres.2015.04.010
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发表时间：
2015-07-01
影响因子：
2.7
通讯作者：
Qiu, Lugui
中科院分区：
文献类型：
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作者：
Li, Fei;Hao, Mu;Qiu, Lugui
位于染色体脆性位点的miRNAs在调节与骨髓瘤发病、疾病进展和耐药性相关的关键基因中发挥重要作用。我们先前的研究结果已经确定miR-33 b（位于染色体17 p）是新诊断的MM患者血清中失调的miRNA之一。然而，关于其在骨髓瘤肿瘤细胞中的表达模式及其在MM患者中的预后价值知之甚少。在本研究中，我们通过定量实时PCR研究了58例新诊断的MM患者，11例复发的MM患者，12例缓解的MM患者和18例健康供体中miR-33 b的表达模式。我们的结果显示，与缓解期患者和健康志愿者相比，新诊断和复发的MM患者中miR-33 b的表达明显下调（p < 0.001）。此外，与没有异常的患者相比，具有del（13 q）、del（17 p）、t（4;14）和高风险遗传异常的患者具有较低的miR-33 b表达水平（p = 0.032、0.018、0.034、0.005）。生存分析显示，miR-33 b低表达患者的PFS（p = 0.016）和OS（p = 0.033）显著缩短，可能与对硼替佐米治疗的耐药相关。我们的数据表明，下调的miR-33 b可能是MM疾病进展和预后不良相关的新预测因子。（C）2015 Elsevier Ltd.版权所有。
MiRNAs located at chromosome fragile sites play important roles in regulating critical genes associated with myeloma pathogenesis, disease progression and drug resistance. Our previous results have identified miR-33b (located in chromosome 17p) was one of the dysregulated miRNAs in the sera of newly diagnosed MM patients. However, little is known about its expression pattern in myeloma tumor cells and its prognostic value in MM patients. In the present study, we investigated the expression pattern of miR-33b in 58 newly diagnosed, 11 relapsed, 12 remission MM patients and 18 health donors by quantitative real-time PCR. Our results showed the expression of miR-33b was obviously down-regulated in newly diagnosed and relapsed MM patients compared to remission patients and health donors (p < 0.001). Moreover, patients with del(13q), del( 17p), t( 4;14) and high-risk genetic abnormalities have lower expression levels of miR-33b compared to patients without those of abnormalities (p = 0.032, 0.018, 0.034, 0.005). Survival analysis showed patients with miR-33b low expression had significantly shortened PFS (p = 0.016) and OS (p = 0.033) and might be associated with drug resistance to bortezomib-based treatment. Our data suggest that down-regulated miR-33b might be a novel predictor associated with disease progression and poor prognosis in MM. (C) 2015 Elsevier Ltd. All rights reserved.