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意义未明的单克隆丙种球蛋白病和多发性骨髓瘤患者血清Dickkopf-1(DKK-1)水平分析

[Analysis of serum levels of Dickkopf-1 (DKK-1) in monoclonal gammopathy of undetermined significance and multiple myeloma].

作者信息

Ščudla Vlastimil, Petrová Pavla, Pika Tomáš, Lochman Pavel, Minařík Jiří, Bačovský Jaroslav, Srovnalík Karel

出版信息

Cas Lek Cesk. 2015;154(4):181-8.

Abstract

BACKGROUND

Several recent studies aim at the detection of biological parameters that enable more precise diagnostics and stratification of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). The objective of our study was to assess the potential contribution of serum levels of Dickkopf-1 (DKK-1) in MGUS and MM from the point of more specific differentiation of both conditions, and the relationship of DKK-1 to selected laboratory parameters, individual forms and clinical stages of both conditions.

METHODS AND RESULTS

The analyzed cohort consisted of 46 individuals with MGUS and 152 patients with MM at the time of diagnosis. For the assessment of serum levels of DKK-1 we used ELISA method. We assessed also serum levels of free light chains (FLC) κ and λ using the Freelite system, and β2-microglobulin (β2-M) using the Immulite 1000 method. For statistical estimation we used: Pearson χ2-test, U-test according to Mann-Whitney and Kruskal-Wallis test. Our analysis revealed that there was no significant difference between the levels of DKK-1 in MGUS risk groups (0-3) and between the states with different FLC concentration including the κ/λ index of monoclonality. In MM there was a significant relationship of DKK-1 to the level of hemoglobin (p<0.008) but not to the levels of FLC, creatinine or β2-microglobulin. Within the Durie-Salmon staging system, there were significant differences of DKK-1 between the stages I vs. III (p=0.001) and I vs. II+III (p=0.002). In the International Staging System (ISS) there were significant differences only between stages 1 vs. 2+3 (p=0.045). Although there was no overall significant difference of DKK-1 levels between MGUS and MM, there was a difference between MGUS vs stage III (p=0.001) and II+III (p=0.001) according to Durie-Salmon, and also MGUS vs. stage 2 (p=0.005) and vs. stages 2+3 (p=0,012) according to ISS. There were no significant differences in DKK-1 between MGUS and initial/asymptomatic form of MM (stage I).

CONCLUSION

Although there was a significant difference of serum levels of DKK-1 between MGUS and initial/asymptomatic stage of MM when compared to advanced stage MM, and in patients with different Hb levels, we do not find the evaluation of serum levels of DKK-1 useful for routine discrimination of MGUS and MM, and for the specification of temporary stratification systems.

摘要

背景

最近的几项研究旨在检测能够更精确地诊断和分层意义未明的单克隆丙种球蛋白病(MGUS)和多发性骨髓瘤(MM)的生物学参数。我们研究的目的是从这两种疾病更特异性的鉴别角度评估Dickkopf-1(DKK-1)血清水平在MGUS和MM中的潜在作用,以及DKK-1与所选实验室参数、这两种疾病的个体形式和临床分期之间的关系。

方法与结果

分析队列包括46例MGUS患者和152例确诊时的MM患者。我们使用ELISA方法评估DKK-1的血清水平。我们还使用Freelite系统评估游离轻链(FLC)κ和λ的血清水平,使用Immulite 1000方法评估β2-微球蛋白(β2-M)。对于统计评估,我们使用:Pearson卡方检验、曼-惠特尼U检验和克鲁斯卡尔-沃利斯检验。我们的分析表明,MGUS风险组(0 - 3)之间的DKK-1水平以及不同FLC浓度状态(包括单克隆性κ/λ指数)之间没有显著差异。在MM中,DKK-1与血红蛋白水平存在显著关系(p<0.008),但与FLC、肌酐或β2-微球蛋白水平无关。在Durie-Salmon分期系统中,I期与III期(p = 0.001)以及I期与II + III期(p = 0.002)之间的DKK-1存在显著差异。在国际分期系统(ISS)中,仅1期与2 + 3期之间存在显著差异(p = 0.045)。尽管MGUS和MM之间的DKK-1水平总体上没有显著差异,但根据Durie-Salmon分期,MGUS与III期(p = 0.001)和II + III期(p = 0.001)之间存在差异,根据ISS,MGUS与2期(p = 0.005)以及与2 + 3期(p = 0.012)之间也存在差异。MGUS与MM的初始/无症状形式(I期)之间的DKK-1没有显著差异。

结论

尽管与晚期MM相比,MGUS和MM的初始/无症状期之间DKK-1的血清水平存在显著差异,并且在不同血红蛋白水平的患者中也存在差异,但我们发现评估DKK-1的血清水平对于MGUS和MM的常规鉴别以及临时分层系统的细化并无用处。

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