Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis.
Serum high expression of miR-214 and miR-135b as novel predictor for myeloma bone disease development and prognosis.
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miR-214和miR-135b的血清高表达作为骨髓瘤骨病发展和预后的新预测因子
DOI：
10.18632/oncotarget.7319
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发表时间：
2016-04-12
期刊：
影响因子：
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通讯作者：
Qiu L
中科院分区：
文献类型：
--
作者：
Hao M;Zang M;Zhao L;Deng S;Xu Y;Qi F;An G;Qin Y;Sui W;Li F;Yang W;Li Z;Yi S;Zou D;Zhan F;Qiu L
多发性骨髓瘤(MM)起源于恶性浆细胞，导致超过80%的MM患者发生多发性破坏性溶骨性病变。MicroRNAs已被报道参与多发性骨髓瘤骨病变的发生发展，然而，作为骨病变诊断和预后生物标志物的循环microRNA尚未阐明。在这项研究中，我们鉴定了MM患者血清中可能与骨髓瘤相关骨病相关的差异表达的miRNAs。MM伴骨病变患者血清MIR-214和miR-135B水平明显升高。血清miR-214和miR-135B水平与溶骨性病变的严重程度高度相关，根据受试者工作特征分析(ROC)的结果，miR-214和miR-135B可作为骨疾病的诊断工具。此外，血清miR-214水平高的患者生存期较短，无进展生存期(PFS)和总生存期(OS)显著缩短。有趣的是，与未接受双膦酸盐治疗的患者相比，接受双膦酸盐治疗的miR-214水平较高的患者的PFS和OS显著延长。总之，我们的研究结果揭示了循环miR-214和miR-135B水平在检测多发性骨髓瘤患者骨疾病和预测预后方面的意义，提示了其潜在的临床应用价值。本研究的结果也为寻找更多的循环miRNA作为肿瘤骨病变的生物标志物奠定了基础。
Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80% of MM patients. MicroRNAs have been reported to be involved in development of bone lesions in MM. However, the circulating microRNA as diagnostic and prognostic biomarkers for bone lesions has not been elucidated yet. In this study, we identified differentially expressed miRNAs that are potentially involved in myeloma-related bone disease in serum of MM patients. MiR-214 and miR-135b was shown to be increased in serum of MM patients with bone lesions. Serum level of miR-214 and miR-135b was highly correlated with the severity of lytic bone lesions and demonstrated as a diagnostic tool for identifying bone diseases based on results of a receiver operating characteristic analysis (ROC). In addition, patients with high levels of serum miR-214 had a dismal survival with significantly shortened progression free survival (PFS) and overall survival (OS). Interestingly, bisphosphonates treatment significantly extended PFS and OS in patients with higher level of miR-214 comparing to patients without bisphosphonates treatment. Taken together, our findings revealed the significance of circulating miR-214 and miR-135b levels in detection of bone disease and in prediction of prognosis of patients with multiple myeloma, suggesting its potential clinical applications. The result of this study also set the foundation for searching more circulating miRNA as biomarker for tumor bone lesions.