Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15771, Athens, Greece.
Laboratory of Clinical Biochemistry-Molecular Diagnostics, Second Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, "P. & A. Kyriakou" Children's Hospital, Athens, Greece.
J Transl Med. 2023 Apr 6;21(1):245. doi: 10.1186/s12967-023-04034-5.
Despite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management.
miRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69). Two external datasets (Kryukov et al. cohort n = 149; MMRF CoMMpass study n = 760) served as institutional-independent validation cohorts. Patients' mortality and disease progression were assessed as clinical endpoints. Internal validation was performed by bootstrap analysis. Clinical benefit was estimated by decision curve analysis.
miRNA-seq highlighted miR-25 of CD138+ plasma cells to be upregulated in MM vs. sMM, R-ISS II/III vs. R-ISS I, and in progressed compared to progression-free patients. The analysis of our screening cohort highlighted that CD138+ miR-25 levels were correlated with short-term progression (HR = 2.729; p = 0.009) and poor survival (HR = 4.581; p = 0.004) of the patients; which was confirmed by Kryukov et al. cohort (HR = 1.878; p = 0.005) and MMRF CoMMpass study (HR = 1.414; p = 0.039) validation cohorts. Moreover, multivariate miR-25-fitted models contributed to superior risk-stratification and clinical benefit in MM prognostication. Finally, elevated miR-25 circulating levels were correlated with poor survival of MM patients (HR = 5.435; p = 0.021), serving as a potent non-invasive molecular prognostic tool.
Our study identified miR-25 overexpression as a powerful independent predictor of poor treatment outcome and post-treatment progression, aiding towards modern non-invasive disease prognosis and personalized treatment decisions.
尽管多发性骨髓瘤（MM）的治疗取得了显著进展，但高度异质性的治疗反应阻碍了可靠的预后和针对性治疗。在此，我们研究了 miRNA 在改善患者管理中的临床应用。
对 24 例 MM 和冒烟型 MM（sMM）患者的骨髓 CD138+浆细胞（PC）进行 miRNA-seq，分析 miRNA 谱。使用内部 RT-qPCR 检测我们的筛选 MM/sMM 队列中的 CD138+和循环 miR-25 水平（CD138+浆细胞 n=167；MM 外周血浆样本亚组 n=69）。两个外部数据集（Kryukov 等人的队列 n=149；MMRF CoMMpass 研究 n=760）作为机构独立验证队列。将患者的死亡率和疾病进展作为临床终点进行评估。内部验证通过自举分析进行。通过决策曲线分析估计临床获益。
miRNA-seq 显示 MM 中 CD138+PC 的 miR-25 上调，与 sMM、R-ISS II/III 与 R-ISS I、进展期与无进展期患者相比。对我们的筛选队列的分析表明，CD138+miR-25 水平与短期进展（HR=2.729；p=0.009）和患者生存不良相关（HR=4.581；p=0.004）；这在 Kryukov 等人的队列（HR=1.878；p=0.005）和 MMRF CoMMpass 研究（HR=1.414；p=0.039）验证队列中得到了证实。此外，多元 miR-25 拟合模型有助于改善 MM 预后中的风险分层和临床获益。最后，循环 miR-25 水平升高与 MM 患者的不良生存相关（HR=5.435；p=0.021），是一种有效的非侵入性分子预后工具。
我们的研究确定了 miR-25 过表达是治疗结果不良和治疗后进展的有力独立预测因子，有助于进行现代非侵入性疾病预后和个性化治疗决策。
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