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

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.

PiwiRNA-651 as marker of treatment response and survival in classical Hodgkin lymphoma

“…Similar results have been observed when studying serum expression of microRNAs in other tumors, including multiple myeloma, where several miRNAs were underexpressed in serum at diagnosis but increased at CR, and lower levels in serum were associated with shorter progression-free survival [44]. In cHL, only one previous study has examined microRNAs in plasma samples, and the authors identified several microRNAs, including miR-494 and miR-1973, whose levels were upregulated at diagnosis and decreased at CR [8].…”

Comparative Analysis of miRNA Expression Profiles of Multiple Myeloma with 1q21 Gains and Normal FISH

“…A decreased level of miR-331 is a marker for shorter progression-free survival in MM [25]. Moreover, downregulation of miR-331-5p and -27a was associated with chemotherapy resistance and relapse in leukaemia [26].…”

Circulating microRNA expressions can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma

“…5 Biological implications of miR-26a, miR-29c and miR-193a have not been studied in MM, but these miRNAs were also suggested as tumor suppressors in hematologic malignancies. For example, miR-193a represses the expression of KIT and its restoration reduces the mRNA and protein levels of KIT in acute myeloid leukemia (AML).…”

“…First, some well-known prognostic miRNA markers of MM [2][3][4][5]15 such as miR-19a were not identified. Since we focused on RRMMs with bortezomib failure and used the miRNA-array which contains just part (381 miRNAs) of the known human miRNAs, there is a possibility that some significant miRNA markers were missed.…”

“…Recently, circulating miRNA has been suggested as a minimally invasive prognostic marker for multiple myeloma (MM) including relapse, which may spare traditional invasive tumor cell examination by bone marrow biopsy. [2][3][4][5] However, circulating miRNA markers associated with the outcomes of Len-dex therapy have not been well studied. A better understanding of these can improve prediction of treatment outcome and selection of therapeutic options in the clinical setting.…”