A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma.

Alfons Navarro,Fabiola Pedrosa,Carlos Fernández De Larrea,Tania Díaz,Natalia Tovar,Rut Tejero,Laura Magnano,Mariano Monzó,María Teresa Cibeira,Joan Bladé,Laura Rosiñol

doi:10.18632/oncotarget.2761

Alfons Navarro, Fabiola Pedrosa + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.2761

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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.

Highlights

Multiple myeloma (MM), a malignant disorder characterized by the neoplastic growth of bone marrow plasma cells, accounts for 15% of all hematologic cancers [1, 2]
MiR-16 and miR-25 have been proposed as independent prognostic markers in newly diagnosed MM [23]. These findings indicate that circulating serum miRNAs are an accessible, stable biomarker that could meet the need for a non-invasive method for monitoring patients with MM
In the subset of 17 patients with paired serum samples at complete response (CR) and at relapse, we examined the expression levels of the miRNAs that had been related to CR or progression-free survival (PFS) in the first part of the validation phase

Summary

Introduction

Multiple myeloma (MM), a malignant disorder characterized by the neoplastic growth of bone marrow plasma cells, accounts for 15% of all hematologic cancers [1, 2]. MM usually progresses from an asymptomatic premalignant state of clonal plasma cell proliferation known as monoclonal gammopathy of undetermined significance (MGUS) [3]. The monitoring of response and progression requires an invasive procedure for the examination of bone marrow, since tumor cells are localized in the marrow and do not usually circulate in blood [5]. Extramedullary disease cannot be accurately evaluated with bone marrow studies [6], and there is a need for non-invasive techniques for both the initial diagnosis and the followup of patients with MM. Serum-free light chain ratio [7] is a well-recognized biomarker for monitoring patients with MM and MGUS, only few other serum-based markers for MM have been incorporated into routine clinical practice

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