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多发性骨髓瘤患者骨病生物标志物Dickkopf-1和硬化蛋白的动态变化

Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma.

作者信息

Gerov Vladimir, Gerova Daniela, Micheva Ilina, Nikolova Miglena, Mihaylova Galya, Galunska Bistra

机构信息

Clinic of Hematology, "St. Marina" University Hospital, 9010 Varna, Bulgaria.

Department of Clinical Laboratory, Faculty of Medicine, Medical University-Varna, 9002 Varna, Bulgaria.

出版信息

J Clin Med. 2023 Jul 1;12(13):4440. doi: 10.3390/jcm12134440.

Abstract

Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 and sclerostin values ( < 0.0001), showing dependence on disease stage (lowest in ISS-I and highest in ISS-III: < 0.0012 and < 0.025, respectively, for both proteins). Bone lesions revealed significant positive correlation with both DKK-1 ( < 0.05) and sclerostin ( < 0.0001). In the course of therapy, significant reduction, more prominent after ASCT, was observed for both parameters in each treatment point compared to the baseline ( < 0.0001). Markedly lower sclerostin ( < 0.01) and DKK-1 ( < 0.05) values were observed in patients with complete and very good partial response compared to those with partial response, stable, or progressive disease. Sclerostin and DKK-1 in NDMM patients reflect the MBD severity and the effect of therapy. Both proteins could represent a novel tool for better disease monitoring and effectiveness of therapy.

摘要

Dickkopf-1(DKK-1)和硬化蛋白是重要的Wnt/β-连环蛋白信号通路抑制剂,在多发性骨髓瘤骨病(MBD)中起重要作用。我们旨在研究新诊断的多发性骨髓瘤(NDMM)患者在诊断时以及治疗过程中,包括自体干细胞移植(ASCT)期间血清DKK-1和硬化蛋白的变化。本研究纳入了41例NDMM患者和33例对照。通过全身低剂量计算机断层扫描评估MBD。使用商用ELISA试剂盒检测DKK-1和硬化蛋白。诊断时,NDMM患者的DKK-1和硬化蛋白值显著更高(<0.0001),显示出对疾病分期的依赖性(国际分期系统[ISS]-I期最低,ISS-III期最高:两种蛋白分别为<0.0012和<0.025)。骨病变与DKK-1(<0.05)和硬化蛋白(<0.0001)均呈显著正相关。在治疗过程中,与基线相比,每个治疗点的这两个参数均显著降低,ASCT后更为明显(<0.0001)。与部分缓解、病情稳定或进展的患者相比,完全缓解和非常好的部分缓解患者的硬化蛋白(<0.01)和DKK-1(<0.05)值明显更低。NDMM患者的硬化蛋白和DKK-1反映了MBD的严重程度和治疗效果。这两种蛋白可能代表了一种更好地监测疾病和评估治疗效果的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f756/10342782/d68f6f50fe55/jcm-12-04440-g001.jpg

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