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硼替佐米为基础方案治疗多发性骨髓瘤患者血清微小 RNA 与早期死亡率的关系。

The Relationship between Serum miRNAs and Early Mortality in Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.

机构信息

Department of Hematology, Medical University of Lodz, 93-510 Lodz, Poland.

Department of Hematooncology, Copernicus Memorial Hospital, 93-510 Lodz, Poland.

出版信息

Int J Mol Sci. 2023 Feb 2;24(3):2938. doi: 10.3390/ijms24032938.

Abstract

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good prognostic markers. The primary aim of this study was to analyze the expression of selected miRNAs in the serum of MM patients who were later treated with bortezomib-based regimens, and to determine their potential to predict early mortality. The study was conducted in 70 prospectively recruited patients with newly diagnosed MM admitted to the Department of Hematology of the Copernicus Memorial Hospital, Lodz (Poland) between 2017 and 2021. Among them, 17 patients experienced death within 12 months of diagnosis. The expression of 31 selected miRNAs was determined using a miRCURY LNA miRNA Custom PCR Panel. The obtained clinical data included patient characteristics on diagnosis, treatment regimen, response to treatment, and follow-up. Differential expression analysis found two miRNAs to be significantly downregulated in the early mortality group: hsa-miR-328-3p (fold change-FC: 0.72, = 0.0342) and hsa-miR-409-3p (FC: 0.49, = 0.0357). Univariate and multivariate logistic regression analyses were performed to assess the early mortality rate. The final model consisted of hsa-miR-409-3p, hsa-miR-328-3p, age, and R-ISS 3. It yielded an area under the curve (AUC) of 0.863 (95%CI: 0.761-0.965) with 88.2% sensitivity and 77.5% specificity. Further external validation of our model is needed to confirm its clinical value.

摘要

多发性骨髓瘤(MM)是一种血液恶性肿瘤,其特征是骨髓(BM)微环境中浆细胞的克隆性增殖。尽管在治疗方面取得了进展,但仍有一些 MM 患者在诊断后的一年内死亡。许多研究调查了 microRNA(miRNA)表达模式,表明它们可能是良好的预后标志物。本研究的主要目的是分析接受硼替佐米为基础的治疗方案治疗的 MM 患者血清中选定 miRNA 的表达,并确定其预测早期死亡率的潜力。该研究在 2017 年至 2021 年期间在波兰罗兹哥白尼纪念医院血液科招募的 70 例新诊断 MM 患者中进行。其中,17 例患者在诊断后 12 个月内死亡。使用 miRCURY LNA miRNA Custom PCR 面板确定了 31 个选定 miRNA 的表达。获得的临床数据包括患者诊断时的特征、治疗方案、治疗反应和随访情况。差异表达分析发现,早期死亡率组有两个 miRNA 显著下调:hsa-miR-328-3p(fold change-FC:0.72, = 0.0342)和 hsa-miR-409-3p(FC:0.49, = 0.0357)。进行了单变量和多变量逻辑回归分析,以评估早期死亡率。最终模型由 hsa-miR-409-3p、hsa-miR-328-3p、年龄和 R-ISS 3 组成。该模型的曲线下面积(AUC)为 0.863(95%CI:0.761-0.965),敏感性为 88.2%,特异性为 77.5%。需要进一步对我们的模型进行外部验证,以确认其临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/593b/9917942/edc8bde46996/ijms-24-02938-g001.jpg

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