Navarro Alfons, Díaz Tania, Tovar Natalia, Pedrosa Fabiola, Tejero Rut, Cibeira María Teresa, Magnano Laura, Rosiñol Laura, Monzó Mariano, Bladé Joan, Fernández de Larrea Carlos
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, 08036 Barcelona, Spain.
Amyloidosis and Myeloma Unit, Department of Hematology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain.
Oncotarget. 2015 Jan 30;6(3):1874-83. doi: 10.18632/oncotarget.2761.
We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT. Supervised analysis identified a differentially expressed 14-microRNA signature. The differential expression of miR-16 (P = 0.028), miR-17 (P = 0.016), miR-19b (P = 0.009), miR-20a (P = 0.017) and miR-660 (P = 0.048) at diagnosis and CR was then confirmed by individual assays. In addition, high levels of miR-25 were related to the presence of oligoclonal bands (P = 0.002). Longer PFS after ASCT was observed in patients with high levels of miR-19b (6 vs. 1.8 years; P < 0.001) or miR-331 (8.6 vs. 2.9 years; P = 0.001). Low expression of both miR-19b and miR-331 in combination was a marker of shorter PFS (HR 5.3; P = 0.033). We have identified a serum microRNA signature with potential as a diagnostic and prognostic tool in MM.
我们检测了多发性骨髓瘤(MM)患者在诊断时以及自体干细胞移植(ASCT)后完全缓解(CR)时的血清微小RNA表达,还检测了意义未明的稳定单克隆丙种球蛋白病患者以及健康对照者的血清微小RNA表达。首先使用TaqMan人类微小RNA阵列对微小RNA进行分析。然后通过单独的TaqMan微小RNA检测对差异表达的微小RNA进行验证,并将其与ASCT后的CR和无进展生存期(PFS)相关联。监督分析确定了一个由14种微小RNA组成的差异表达特征。随后通过单独检测证实了miR-16(P = 0.028)、miR-17(P = 0.016)、miR-19b(P = 0.009)、miR-20a(P = 0.017)和miR-660(P = 0.048)在诊断和CR时的差异表达。此外,高水平的miR-25与寡克隆带的存在相关(P = 0.002)。在miR-19b水平高的患者中观察到ASCT后更长的PFS(6年对1.8年;P < 0.001),在miR-331水平高的患者中也观察到更长的PFS(8.6年对2.9年;P = 0.001)。miR-19b和miR-331两者低表达共同是PFS较短的一个标志物(风险比5.3;P = 0.033)。我们已经确定了一种血清微小RNA特征,其有潜力作为MM的诊断和预后工具。