血清HMGB1、sRAGE在初诊多发性骨髓瘤的诊断、疗效监测及预后中的价值

The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma

目的:评估血清高迁移率族蛋白B1(HMGB1)、可溶性晚期糖基化终末产物受体(s RAGE)对初诊多发性骨髓瘤(MM)的诊断、疗效监测及预后价值。方法:采用酶联免疫吸附实验(ELISA)检测2018年10月至2020年5月收治的50例初诊MM患者化疗前后及50例血液科门诊就诊者的血清HMGB1、s RAGE水平,用ROC进一步分析血清HMGB1、s RAGE水平对MM诊断的效能;同时,比较化疗前后血清HMGB1、s RAGE水平,分析其在MM患者疗效评估中的价值,并分别根据血清HMGB1、s RAGE水平的均值进行分组,对所有患者进行跟踪,比较患者的临床特点及生存状况。结果:治疗前MM组患者血清HMGB1水平高于对照组,s RAGE水平低于对照组(t=11.363、6.127,P<0.001),分别单独应用血清HMGB1、s RAGE检测诊断MM患者的AUC为0.955、0.811。经3个疗程化疗后,CR组患者的HMGB1水平较化疗前低,PD组患者的HMGB1水平较化疗前明显升高,PR组患者的s RAGE水平较化疗前明显升高(P<0.05)。HMGB1低表达组(25例)和HMGB1高表达组(25例)的患者相比,在R-ISS分期、HGB、CRP、ESR、CD56、CD117、D13S319缺失等方面均有统计学差异(χ^(2)=3.920、6.522、6.65、4.16、3.945、6.65、4.16,P<0.05);s RAGE低表达组(28例)和s RAGE高表达组(22例)的患者相比,在ISS分期、CRP、CD56等方面均有统计学差异(χ^(2)=4.565、4.711、5.547,P<0.05)。Kaplan-Meier生存分析显示HMGB1低表达组患者的存活状况更好,PFS比较结果为T_(低表达组)>T_(高表达组)(χ^(2)=9.470,P<0.05),OS表达结果为T低表达组>T高表达组(χ^(2)=7.808,P<0.05);s RAGE高表达组的存活状况与低表达组比较无差异,PFS比较结果为T_(低表达组)<T_(高表达组)(χ^(2)=1.661,P>0.05),OS比较结果为T_(低表达组)<T_(高表达组)(χ^(2)=2.048,P>0.05)。Cox分析显示LDH、HMGB1均是患者预后的影响因素,两者均影响患者的PFS(HR=2.771,95%CI:1.002-7.662,P=0.049;HR=6.022,95%CI:1.689-21.470,P=0.006),HMGB1也是影响患者OS(HR=4.275,95%CI:1.183-15.451,P=0.027)的因素。结论:血清HMGB1、s RAGE对初诊MM患者的诊断、疗效监测均有一定的辅助价值,血清HMGB1有望成为MM预后的辅助检测指标。

Objective:To evaluate the value of high mobility group protein B1(HMGB1)and soluble receptor for advanced glycation end products(s RAGE)in the diagnosis,efficacy monitoring and prognosis of newly diagnosed multiple myeloma(MM)patients.Methods:Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected.Enzyme linked immunosorbent assay(ELISA)was used to detect the serum HMGB1 and s RAGE levels of the patients.ROC was used to further analyze the efficacy of serum HMGB1 and s RAGE levels on the diagnosis of MM.At the same time,the serum levels of HMGB1 and s RAGE before and after chemotherapy were compared,and their values in the evaluation of curative effect of MM patients were analyzed.According to the mean values of serum HMGB1 and s RAGE,all the patients were divided into different groups,the clinical characteristics and survival status of the patients were compared.Results:Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group,while s RAGE level was lower(t=11.363,6.127,P<0.001).The AUC of serum HMGB1 and s RAGE in the MM patients was 0.955 and 0.811,respectively.After 3 courses of chemotherapy,HMGB1 level of the patients in CR group was lower than before chemotherapy,while in PD group was higher,as well as s RAGE level of the patients in PR group(P<0.05).There were significant differences in R-ISS stage,HGB,CRP,ESR,CD56,CD117,D13 S319 deletion between HMGB1 high expression group and HMGB1 low expression group(χ^(2)=3.920,6.522,6.65,4.16,3.945,6.65,4.16,P<0.05),while there were significant differences in ISS stage,CRP and CD56 between s RAGE low expression group(28 cases)and s RAGE high expression group(22 cases)(χ^(2)=4.565,4.711,5.547,P<0.05).Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition,for PFS T_(low)>T_(high)(χ^(2)=9.470,P<0.05),and for OS Tlow>Thigh(χ^(2)=7.808,P<0.05);there was no difference in the survival of s RAGE high expression group and low expression group,for PFS T_(low)<T_(high)(χ^(2)=1.661,P>0.05),and for OS T_(low)<T_(high)(χ^(2)=2.048,P>0.05).Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients,and both of them affected PFS(HR=2.771,95%CI:1.002-7.662,P=0.049;HR=6.022,95%CI:1.689-21.470,P=0.006),while HMGB1 also affected OS(HR=4.275,95%CI:1.183-15.451,P=0.027).Conclusion:The serum HMGB1 and s RAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients,and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.