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A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma
Authors:Alfons Navarro  Tania Díaz  Natalia Tovar  Fabiola Pedrosa  Rut Tejero  María Teresa Cibeira  Laura Magnano  Laura Rosi?ol  Mariano Monzó   Joan Bladé   Carlos Fernández de Larrea
Affiliation:1. Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, 08036 Barcelona, Spain;2. 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
Abstract:
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.
Keywords:miRNA   serum   myeloma   autologous transplantation   complete remission
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