Identification of a novel microRNA, miR-4449, as a potential blood based marker in multiple myeloma.

Background: miRNAs act in diverse biological processes including development, cell growth, apoptosis, and hematopoiesis, suggesting their role in cancer. Methods: We examined the miRNAs perturbed in CD138+ primary multiple myeloma (MM) cells, using microarray analysis and real-time quantitative PCR (RT-qPCR). Serum miR-4449 expression levels were detected from 71 primary MM patients and 46 healthy controls by RT-qPCR. Results: Our analysis revealed up-regulation of 54 and down-regulation of 28 miRNAs in MM subjects compared to healthy controls. miR-4449 has not been reported in MM. It was found that the relative expression of bone marrow miR-4449 in MM patients (2.14±1.42) was higher than that in healthy controls (0.815±0.165) (U = 8, p = 0.0093). The relative expression of serum miR-4449 in MM patients (2.11±2.10) was significantly higher than that in healthy controls (0.357±0.235) (U = 374, p < 0.0001) and was significantly correlated with β₂M, λ light and к light chain concentration (r = 0.480, p = 0.0003; r = 0.560, p < 0.0001; r = 0.560, p < 0.0001), but not correlated with the lactate dehydrogenase (LDH) concentration (r = 0.247, p = 0.0611). The area under the curve (AUC) of the receiver-operating characteristics (ROC) curve of serum miR-4449 was 0.885 (95% CI, 0.826-0.945), which is higher than for other markers. Combining miR- 4449, λ light chain, and β₂M together, the sensitivity was highest compared with λ light chain or β2M alone, or combined.Conclusions: The expression levels of serum miR-4449 in MM patients were significantly higher than in healthy controls, suggesting that it may prove to be useful in the auxiliary diagnosis of MM. [ABSTRACT FROM AUTHOR]