| Description |
Introduction: MicroRNAs (miRNAs) are involved in the pathogenesis of multiple myeloma (MM) and could be involved in forms of extramedullary MM (EM). Circulating miRNAs are stable, quantifiable in body fluids and have the potential to become a diagnostic marker for MM. The aim of this study was to identify circulating miRNA able to distinguish patients with MM and EM from healthy donors (HD) using TaqMan Low Density Arrays (TLDA) and quantitative PCR (qPCR) and compare deregulated miRNA expression levels with clinical parameters. Methods: The study included 118 sera. TLDA screening 667 miRNA was performed on serum samples of 5 EM, 5 newly diagnosed MM and 6 HD. Selected differentially expressed miRNAs (p<0.05) between groups were verified using qPCR using absolute quantification by 35 EM, 35 newly diagnosed MM, 18 MM in relapse / progression and HD 30. Furthermore, ROC analysis was performed miRNA monitored and correlated with biochemical parameters in EM and MM. Results: MiRNA profiling revealed 14 deregulated miRNAs (all p<0.05, after correction p<0.41) between MM and EM and 20 deregulated miRNAs between EM and HD (all p<0.05, after correction for p<0,40). The expression levels of miR-222, miR-130a, miR-34a and miR-195 were further validated in a larger sample set. The level of miR-130a was significantly reduced, miR-222 and miR-34a conversely increased in EM comparison with the HD (all p<0.005); In addition, miR-130a was reduced and miR-34a increased in EM compared to newly diagnosed MM (p<0.06), but compared to MM in relapse / progression, only miR-130a remained significantly reduced. MiR-130a distinguished from EM to HD specificity of 90.0%, a sensitivity of 74.3% at a cut-off value of 3377 (number of molecules per 1 ng of total miRNA / RNA), followed by EM newly diagnosed with MM, specificity 94.3%, sensitivity of 28.6%, at a cut-off value of 1438 by EM and MM in relapse / progression with a specificity of 94.4%, a sensitivity of 28.6% at the same cut-off value. The EM file miR-130a positively correlated with hemoglobin levels and platelet counts (rs=0.397 and 0.439, all p<0.05) and negatively with the level of monoclonal immunoglobulin, beta-2-microglobulin and C-reactive protein (rs = 0.398, -0.427 and -0.488, all p<0.05). The level of expression of this miRNA was in association with a higher stage ISS (p=0.017). Conclusion: Our results show that serum miR-130a could be a marker for patients with EM form of MM.
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