文章：

完善多发性骨髓瘤的精准预后评估：CD138+浆细胞中miR-221/222簇缺失导致短期进展和较差的治疗结局

Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome

原文发布日期：2025-03-15

DOI: 10.1038/s41408-025-01248-2

类型: Article

开放获取: 是

英文摘要：

The persistence of high relapse rates and therapy resistance continues to challenge the effective management of multiple myeloma (MM). The identification of novel MM-specific molecular markers could ameliorate risk-stratification tools and accurately identify high-risk patients towards personalized prognosis and therapy. miRNA-seq analysis of CD138+ plasma cells (n = 24) unveiled miR-221-3p and miR-222-3p (miR-221/222 cluster) as the most downregulated miRNAs in R-ISS III compared to R-ISS I/II patients. Subsequently, miR-221/222 levels were quantified by RT-qPCR in CD138+ plasma cells of our screening cohort (n = 141), assessing patients’ mortality and disease progression as clinical endpoints. Internal validation was performed by bootstrap analysis, while clinical benefit was estimated by decision curve analysis. Kryukov et al. (n = 149) and Aass et al. (n = 86) served as institutional-independent validation cohorts. Loss of miR-221/222 cluster was strongly associated with patients’ short-term progression and poor overall survival, which was confirmed by Kryukov et al. and Aass et al. validation cohorts. Intriguingly, miR-221/222-fitted multivariate models offered superior risk-stratification within R-ISS staging and risk-based cytogenetics. Moreover, miR-221/222 loss could effectively discriminate optimal 1st-line treatment responders with inferior treatment outcome. Our study identified the loss of miR-221/222 cluster as a powerful independent predictor of patients’ post-treatment progression, ameliorating prognosis and supporting precision medicine in MM.
 

摘要翻译： 

多发性骨髓瘤（MM）的高复发率和治疗耐药性问题持续存在，对其有效管理构成挑战。识别新型MM特异性分子标志物可优化风险分层工具，精准识别高风险患者以实现个体化预后评估与治疗。通过对CD138+浆细胞（n=24）进行miRNA测序分析，发现与R-ISS I/II期患者相比，R-ISS III期患者中miR-221-3p和miR-222-3p（miR-221/222簇）表达下调最为显著。随后在我们筛选队列（n=141）的CD138+浆细胞中通过RT-qPCR定量检测miR-221/222表达水平，以患者死亡率和疾病进展作为临床终点进行评估。采用Bootstrap分析进行内部验证，并通过决策曲线分析评估临床获益。Kryukov等人（n=149）和Aass等人（n=86）的研究队列作为独立机构验证集。miR-221/222簇的表达缺失与患者短期进展及不良总生存期密切相关，该结果在Kryukov和Aass验证队列中得到证实。值得注意的是，整合miR-221/222的多变量模型能在R-ISS分期和基于细胞遗传学的风险分层中提供更优的风险评估。此外，miR-221/222缺失能有效甄别一线治疗反应不佳的患者群体。本研究证实miR-221/222簇的表达缺失是预测患者治疗后疾病进展的强效独立指标，可改善预后评估并支持多发性骨髓瘤的精准医疗实践。

原文链接：

Refining precision prognostics in multiple myeloma: loss of miR-221/222 cluster in CD138+ plasma cells results in short-term progression and worse treatment outcome