Papanota Aristea-Maria, Tsiakanikas Panagiotis, Kontos Christos K, Malandrakis Panagiotis, Liacos Christine-Ivy, Ntanasis-Stathopoulos Ioannis, Kanellias Nikolaos, Gavriatopoulou Maria, Kastritis Efstathios, Avgeris Margaritis, Dimopoulos Meletios-Athanasios, Scorilas Andreas, Terpos Evangelos
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece.
Cancers (Basel). 2021 Jul 31;13(15):3877. doi: 10.3390/cancers13153877.
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.
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.
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.
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.
多发性骨髓瘤骨病（MMBD）是多发性骨髓瘤（MM）常见且严重的并发症，影响生活质量和生存期。我们评估了一组19种与骨质疏松相关的微小RNA（miRNA）在MMBD中的临床价值。
从62例新诊断的有或无MMBD的MM患者血浆中分离miRNA。合成第一链cDNA，并使用qPCR进行相对定量。最后，我们进行了广泛的生物统计学分析。
与无MMBD的MM患者相比，有MMBD的MM患者血浆中let-7b-5p、miR-143-3p、miR-17-5p、miR-214-3p和miR-335-5p的循环水平显著更高。受试者工作特征曲线和逻辑回归分析表明，这些miRNA可以准确预测MMBD。此外，基于多miRNA的独立逻辑回归模型在预测MMBD方面表现出最佳潜力。生存分析表明，其中两种miRNA在MM中也具有预后作用，因为较低的let-7b-5p和miR-335-5p循环水平与显著更差的无进展生存期相关，独立于既定的预后因素。
我们的研究提出了一种miRNA特征以促进MMBD诊断，尤其是在不明确的病例中。此外，我们提供了let-7b-5p和miR-335-5p作为MM中非侵入性预后生物标志物的预后作用的证据。
