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多发性骨髓瘤中可溶性尿激酶型纤溶酶原激活物受体分析用于预测预后

Analysis of soluble urokinase plasminogen activator receptor in multiple myeloma for predicting prognosis.

作者信息

Shen Jie, Wang Qing, Wang Juan, Su Guo-Hong, Wang Juan, Guo Sheng-Hu, Liu Y A, Wu Zheng, Liu Rong-Feng, Li Xing, Guo Xiao-Jin, Cao Jing, Zhang Yue-Hua, Wang Zhi-Yu

机构信息

Department of Immunology and Immunotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China ; Department of Hematology, Centre Hospital of Cangzhou, Cangzhou, Hebei 061001, P.R. China.

Department of Hematology, Centre Hospital of Cangzhou, Cangzhou, Hebei 061001, P.R. China.

出版信息

Oncol Lett. 2015 Oct;10(4):2403-2409. doi: 10.3892/ol.2015.3613. Epub 2015 Aug 14.

Abstract

Multiple myeloma is a type of malignancy, which affects the plasma cells of the bone marrow. Recent studies have found that malignant plasma cells may express urokinase plasminogen activator (uPA) and uPA receptor (uPAR), and that initiation of proteolytic events by this system contributes to the process of invasion and destruction of the bone marrow. Studies have also suggested that the level of the soluble form of uPAR (suPAR) may act as a marker for prognosis in patients with multiple myeloma, and that there is an association between uPAR/suPAR expression, and clinical characteristics, efficacy of treatment in disease control and patient survival. In order to investigate this, the present study used flow cytometry to detect the monoclonal antibodies associated with multiple myeloma, specifically, uPAR (CD87), CD56 and CD38. Patients with multiple myeloma were divided into the following groups: The effective groups (remission and stable disease) and the ineffective group (progressive disease). suPAR expression in the effective groups was 257.6±32.47 pg/ml and 331.0±99.80 pg/ml respectively, which was not significantly different from that of the normal control group (P>0.05). By contrast, the suPAR level in the invalid group was 562.2±291.0 pg/ml, which was significantly different from the levels in the normal control group (P<0.01) and the effective groups (P<0.05). suPAR levels were positively correlated with disease stage (P<0.01), renal function (P<0.05), C-reactive protein (P<0.005), β2-microglobulin (P<0.001), extramedullary involvement (P<0.001), chromosome 13 deletion (P<0.01) and survival >2 years (P<0.01). They were was negatively correlated with hemoglobin concentration. No correlation was observed between uPAR expression and suPAR levels. The present study also indicated that the stage of disease and suPAR expression were independent factors, which predicted survival of <2 years. In conclusion, high suPAR expression appears to predict disease progression, a shortened survival period and early extramedullary infiltration.

摘要

多发性骨髓瘤是一种恶性肿瘤,会影响骨髓中的浆细胞。最近的研究发现,恶性浆细胞可能表达尿激酶型纤溶酶原激活剂(uPA)和uPA受体(uPAR),并且该系统引发的蛋白水解事件有助于骨髓的侵袭和破坏过程。研究还表明,可溶性uPAR(suPAR)水平可能作为多发性骨髓瘤患者预后的标志物,并且uPAR/suPAR表达与临床特征、疾病控制中的治疗效果和患者生存率之间存在关联。为了对此进行研究,本研究使用流式细胞术检测与多发性骨髓瘤相关的单克隆抗体,具体而言,即uPAR(CD87)、CD56和CD38。将多发性骨髓瘤患者分为以下几组:有效组(缓解期和疾病稳定期)和无效组(疾病进展期)。有效组中的suPAR表达分别为257.6±32.47 pg/ml和331.0±99.80 pg/ml,与正常对照组相比无显著差异(P>0.05)。相比之下,无效组中的suPAR水平为562.2±291.0 pg/ml,与正常对照组(P<0.01)和有效组(P<0.05)的水平有显著差异。suPAR水平与疾病分期(P<0.01)、肾功能(P<0.05)、C反应蛋白(P<0.005)、β2微球蛋白(P<0.001)、髓外受累(P<0.001)、13号染色体缺失(P<0.01)和生存>2年(P<0.01)呈正相关。它们与血红蛋白浓度呈负相关。未观察到uPAR表达与suPAR水平之间的相关性。本研究还表明,疾病分期和suPAR表达是预测生存<2年的独立因素。总之,高suPAR表达似乎预示着疾病进展、生存期缩短和早期髓外浸润。

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