Bergantim Rui, Peixoto da Silva Sara, Pinto Vanessa, Pereira Joana M, Sousa Diana, Trigo Fernanda, Matthiesen Rune, Guimarães José E, Vasconcelos M Helena
i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Front Pharmacol. 2025 Apr 4;16:1465814. doi: 10.3389/fphar.2025.1465814. eCollection 2025.
Multiple myeloma (MM) is a complex hematological malignancy with heterogeneous clinical and pathophysiological backgrounds that influence treatment responses and outcomes. Identifying biomarkers to predict drug response and guide treatment decisions, particularly regarding drug combinations, is essential to improve therapeutic efficacy and patient outcomes. This study explores the role of microRNAs (miRNAs/miRs) derived from bone marrow (BM) and peripheral blood (PB) in responses to treatment and survival outcomes in newly diagnosed MM (ndMM) patients.
This study included twenty patients with ndMM undergoing first-line treatment with bortezomib, thalidomide, and dexamethasone. The miRNAs were isolated from BM and PB, and their profiles were analyzed using Next-Generation Sequencing (NGS), followed by validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR). Clinical and response data were collected to assess correlations between miRNA levels, clinical characteristics, and patient outcomes. analysis for target-prediction and gene ontology (GO) enrichment was performed to explore the potential biological and functional role of the identified miRNAs.
NGS profiling revealed several miRNAs differently expressed between treatment-refractory and sensitive patients, as well as between PB and BM. Among these, miR-665, miR-483-5p, miR-143-3p and miR-145-5p were selected for further validation by qPCR. It was observed that miR-665 was significantly elevated in treatment-refractory patients compared to treatment-sensitive patients. Additionally, miR-665 levels were higher in PB than in BM. Elevated miR-665 levels were associated with more aggressive disease characteristics and poorer clinical outcomes, including reduced overall survival.
Our preliminary findings suggest that miR-665 could potentially serve as a non-invasive tool for predicting drug resistance and guiding treatment decisions in MM. These findings also highlight the potential utility of miRNAs in liquid biopsies as a predictive tool of drug response in MM and could pave the way for personalized treatment strategies, improving patient outcomes. Future research is needed to validate these results in larger cohorts and explore the underlying mechanisms of miR-665 in MM pathogenesis and drug resistance.
多发性骨髓瘤（MM）是一种复杂的血液系统恶性肿瘤，具有异质性的临床和病理生理背景，这些背景会影响治疗反应和结果。识别生物标志物以预测药物反应并指导治疗决策，尤其是关于药物联合使用的决策，对于提高治疗效果和患者预后至关重要。本研究探讨了源自骨髓（BM）和外周血（PB）的微小RNA（miRNA/miR）在新诊断的MM（ndMM）患者治疗反应和生存结果中的作用。
本研究纳入了20例接受硼替佐米、沙利度胺和地塞米松一线治疗的ndMM患者。从BM和PB中分离出miRNA，并使用下一代测序（NGS）分析其谱，随后通过定量实时PCR（qPCR）验证差异表达的miRNA。收集临床和反应数据以评估miRNA水平、临床特征和患者结果之间的相关性。进行靶标预测和基因本体（GO）富集分析，以探索所鉴定miRNA的潜在生物学和功能作用。
NGS分析显示，在治疗难治性和敏感患者之间以及PB和BM之间，有几种miRNA表达不同。其中，选择miR-665、miR-483-5p、miR-143-3p和miR-145-5p通过qPCR进行进一步验证。观察到与治疗敏感患者相比，miR-665在治疗难治性患者中显著升高。此外，PB中的miR-665水平高于BM。miR-665水平升高与更具侵袭性的疾病特征和更差的临床结果相关，包括总生存期缩短。
我们的初步研究结果表明，miR-665可能潜在地作为一种非侵入性工具，用于预测MM中的耐药性并指导治疗决策。这些发现还突出了miRNA在液体活检中作为MM药物反应预测工具的潜在效用，并可能为个性化治疗策略铺平道路，改善患者预后。未来需要进行更多研究，以在更大的队列中验证这些结果，并探索miR-665在MM发病机制和耐药性中的潜在机制。
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