多发性骨髓瘤患者骨髓骨硬化蛋白和核因子-κB受体活化因子表达及临床意义

Expression and Clinical Significance of Sclerostin and RANKL in Multiple Myeloma Patients

目的:探讨多发性骨髓瘤(MM)患者骨髓上清液中骨硬化蛋白(Sclerostin)和核因子-κB受体活化因子(RANKL)表达水平及其临床意义。方法:收集2018年1月至2020年6月就诊的60例多发性骨髓瘤患者作为研究对象,基于国际分期系统(ISS)分期将多发性骨髓瘤患者分为ISSⅠ期、Ⅱ期和Ⅲ期,其中ISSⅠ期患者18例,ISSⅡ期患者23例,ISSⅢ期患者19例。同时将同期通过骨髓穿刺证明其骨髓功能正常且无血液系统病症的58例健康人群作为对照组。收集整理多发性骨髓瘤患者的年龄、性别、体重指数、校正血钙、骨损伤、C反应蛋白和乳酸脱氢酶等临床病理资料,检测并对比多发性骨髓瘤组和对照组骨髓骨硬化蛋白及RANKL表达水平。分析不同ISS分期的多发性骨髓瘤患者骨髓骨硬化蛋白和RANKL表达水平;采用Pearson等级相关分析多发性骨髓瘤患者骨髓骨硬化蛋白和RANKL表达水平相关性;采用Kaplan-Meier法分析骨髓骨硬化蛋白和RANKL表达水平与多发性骨髓瘤患者3年生存率的关系。结果:与对照组相比,多发性骨髓瘤组骨髓骨硬化蛋白和RANKL表达水平均显著升高(P<0.05)。多发性骨髓瘤患者临床病理特征结果显示,患者骨髓骨硬化蛋白和RANKL表达水平与校正血钙、C反应蛋白和乳酸脱氢酶等密切相关(P<0.05)。不同ISS分期的多发性骨髓瘤患者骨髓骨硬化蛋白和RANKL表达水平差异有统计学意义(P<0.05),与ISSⅠ期和Ⅱ期患者相比,ISSⅢ期患者骨髓骨硬化蛋白和RANKL表达水平显著升高(P<0.05),ISSⅡ期患者骨髓骨硬化蛋白和RANKL表达水平显著高于ISSⅠ期多发性骨髓瘤患者(P<0.05)。Pearson等级相关分析显示,多发性骨髓瘤患者骨髓骨硬化蛋白和RANKL表达水平正相关(r=0.551,P<0.001)。Kaplan-Meier结果显示骨髓骨硬化蛋白高表达者的3年生存率低于骨硬化蛋白低表达者(χ^(2)=3.916,P<0.05),骨髓RANKL高表达的多发性骨髓瘤患者3年生存率低于RANKL低表达患者(χ^(2)=4.223,P<0.05)。结论:多发性骨髓瘤患者骨髓骨硬化蛋白和RANKL表达水平显著升高,且二者对于预测多发性骨髓瘤患者预后具有重要的临床应用价值。

Objective:To investigate the expression levels of sclerostin and receptor activator of NF-κB ligand(RANKL)in bone marrow supernatant of multiple myeloma(MM)patients and their clinical significance.Methods:60 patients with MM from January 2018 to June 2020 were collected as research objects.Based on the International Staging System(ISS),patients with MM were divided into ISS stageⅠ,ⅡandⅢstages,including 18 patients with ISS stageⅠ,23 patients with ISS stageⅡand 19 patients with ISS stageⅢ.At the same time,58 patients who proved that their bone marrow function was normal through bone marrow aspiration and non-hematological diseases were included as the control group.The clinicopathological data of MM patients including age,sex,body mass index(BMI),corrected blood calcium,bone injury,C-reactive protein and lactate dehydrogenase were collected and sorted.The expression levels of sclerostin and RANKL in bone marrow of MM group and control group were detected and compared.The expression levels of sclerostin and RANKL in bone marrow of MM patients with different ISS stages were analyzed.The correlation between the expression levels of RANKL and sclerostin in bone marrow of MM patients was analyzed by Pearson grade correlation.Kaplan-Meier method was used to analyze the relationship between the expression levels of sclerostin and RANKL in bone marrow and the three-year survival rate of MM patients.Results:Compared with control group,the expression levels of sclerostin and RANKL in bone marrow of MM group were significantly increased(P<0.05).The clinicopathological characteristics of MM patients showed that the expression levels of sclerostin and RANKL in bone marrow were closely correlated with corrected blood calcium,C-reactive protein and lactate dehydrogenase(P<0.05).There were significant differences in the expression levels of bone marrow sclerostin and RANKL in MM patients with different ISS stages(P<0.05).Compared with patients with ISS stageⅠandⅡ,the expression levels of bone marrow sclerostin and RANKL were significantly increased in patients with ISS stageⅢ(P<0.05).The expression levels of sclerostin and RANKL in bone marrow of ISS stageⅡpatients were significantly higher than those of ISS stageⅠMM patients(P<0.05).Pearson grade correlation analysis showed that the expression levels of bone marrow sclerostin and RANKL were positively correlated in MM patients(r=0.551,P<0.001).Kaplan-Meier results showed that the 3-year survival rate of patients with high expression of sclerostin in bone marrow was lower than that of patients with low expression of RANKL(χ^(2)=3.916,P<0.05),and the 3-year survival rate of patients with high expression of RANKL in bone marrow was lower than that of patients with low expression of RANKL(χ^(2)=4.223,P<0.05).Conclusion:The expression levels of sclerostin and RANKL in bone marrow of MM patients were significantly increased,and both of them had important clinical application value in predicting the prognosis of MM patients.