| Description |
Introduction: MicroRNAs (miRNA), short non-coding RNAs, are involved in the pathogenesis of multiple myeloma (MM), and it is possible that they are involved in formation of mold MM extramedullary (EM). Circulating miRNAs are stable, quantifiable in body fluids and have the potential to become a diagnostic marker, as previously shown by MM. The aim of this study was to identify the profile of circulating miRNAs using TaqMan Low Density Arrays (TLDA) and quantitative PCR (qPCR) for patients with EM, MM and healthy donors (HD) and compare the expression levels of miRNAs deregulated with clinical parameters. Methods: In total, the study included 100 serum samples from EM patients newly diagnosed MM patients and HD. TLDA screening 667 miRNA was performed on 5 EM, 5 MM, and 6 HD. Selected differentially expressed miRNAs (p<0.05) between samples EM and MM and between EM and HD were confirmed by qPCR using the absolute quantification in 35 EM, 35 MM and 30 HD. ROC analysis was performed each reference miRNA and their combination and correlation 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 EM, MM and HD. 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); Moreover, miR-130a was reduced, and miR-34a is increased EM compared with MM (p<0.06). ROC analysis of the combination of miR-130a and miR-34a distinguish EM from HD with a sensitivity of 74.3%, a specificity of 90% and AUC=0.879. Furthermore, such a combination of miRNA compared with MM differentiate EM EM sensitivity 54.3%, specificity 80%, and AUC=0.675. In 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 the miRNA associate with higher stage ISS (p=0.017). MiR-222 was positively correlated with the level of lactate dehydrogenase (rs = 0.417, p<0.05); miR-222 and miR-34a were positive association with the percentage of bone marrow infiltration by plasma cells (rs=0.435 and 0.562, p<0.05). Conclusion: Our results show that serum miR-130a and miR-34a could become promising biomarker patients with extramedullary form of MM.
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