Clinical Research Papers:
A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma
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Alfons Navarro1, Tania Díaz2, Natalia Tovar2, Fabiola Pedrosa2, Rut Tejero1, María Teresa Cibeira2, Laura Magnano2, Laura Rosiñol2, Mariano Monzó1, Joan Bladé2, Carlos Fernández de Larrea2
1Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, 08036 Barcelona, Spain
2Amyloidosis 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
Carlos Fernández de Larrea, e-mail: [email protected]
Keywords: miRNA, serum, myeloma, autologous transplantation, complete remission
Received: October 26, 2014 Accepted: November 17, 2014 Published: January 22, 2015
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.
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