A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Simple Summary Multiple myeloma bone disease (MMBD) is one of the most important complications of multiple myeloma with a great impact on quality of life. Recent advances in the field of imaging techniques provided clinicians with a variety of imaging modalities with high sensitivity for the diagnosis of MMBD. However, no circulating biomarkers are available to support the diagnosis of MMBD in cases where the results are inconclusive. The aim of our study was to investigate the clinical utility of 19 miRNAs implicated in osteoporosis in MMBD. Our results suggest that the levels of circulating let-7b-5p, miR-143-3p, miR-17-5p, miR-335-5p, and miR-214-3p (standalone or combined in multi-miRNA models) can effectively predict the presence of MMBD in newly diagnosed MM patients. Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA-based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.