多发性骨髓瘤患者骨髓组织NAMPT的表达及临床意义

Expression and Clinical Significance of NAMPT in Bone Marrow of Patients with Multiple Myeloma

目的:研究烟酰胺磷酸核糖转移酶(NAMPT)在多发性骨髓瘤中的表达水平、与临床指标和预后的关系及可能潜在的作用。方法:采用免疫组化染色检测初治多发性骨髓瘤(NDMM)患者与同期住院的缺铁性贫血患者骨髓活检组织的NAMPT表达情况。根据NAMPT中位表达水平将NDMM患者分为高表达组与低表达组,分析NAMPT表达水平与临床基线数据的相关性,并进行生存分析,评估NAMPT表达量与患者预后的关系。GSE24080、GSE19784数据集生信分析NAMPT对患者预后的影响,基因集富集分析探讨NAMPT参与多发性骨髓瘤细胞功能的可能机制。结果:31例NDMM患者骨髓组织NAMPT的平均染色强度为0.007±0.002,10例缺铁性贫血患者为0.002±0.002(P<0.05)。将NDMM患者以NAMPT的中位数0.0041为界分组,高表达组与低表达组的平均染色强度分别为0.007±0.005和0.002±0.001(P<0.001);高表达与低表达组乳酸脱氢酶、C反应蛋白及ISS分期比较有差异(P<0.001),其余指标无差异;高表达组的总体反应率显著低于低表达组(P<0.001);高表达组的中位生存时间显著短于低表达组(P=0.024)。生信分析结果显示,与NAMPT高表达组相比,低表达组的无事件生存率和总生存率更高(P=0.037,P=0.009),并且NAMPT表达是NDMM患者无事件生存率和总生存率的独立预后因素(P=0.006,P=0.020)。基因集富集分析结果表明,NAMPT可能通过m TORC1信号通路影响多发性骨髓瘤细胞功能。结论:NDMM患者骨髓NAMPT表达量显著高于缺铁性贫血患者,高表达NAMPT可能与ISS分期较晚、乳酸脱氢酶和C反应蛋白水平较高具有相关性。NAMPT高表达患者对硼替佐米的治疗反应更差,生存时间可能更短。NAMPT可能通过m TORC1信号通路参与多发性骨髓瘤的发生与发展。

Objective:To study the expression level of nicotinamide phosphoribosyltransferase(NAMPT) in multiple myeloma(MM),its relationship with clinical indicators,prognosis and potential role.Methods:Immunohistochemical staining was used to detect the expression of NAMPT in bone marrow biopsies of patients with newly diagnosed multiple myeloma(NDMM) and patients with iron deficiency anemia(IDA) hospitalized during the same period.According to the median expression level of NAMPT,NDMM patients were divided into high expression group and low expression group.The correlation between NAMPT expression level and clinical baseline data was analyzed,and survival analysis was performed to evaluate the relationship between NAMPT expression level and prognosis.The GSE24080 and GSE19784datasets were used to analyze the effect of NAMPT on the prognosis.Gene set enrichment analysis(GSEA) explored the possible mechanism of NAMPT involved in MM cell function.Results:The mean staining intensity of NAMPT in bone marrow tissue of 31 NDMM patients was 0.007±0.002,and that of 10 IDA patients was 0.002±0.002(P<0.05).The median expression level of NAMPT was 0.0041 in NDMM patients,and the mean staining intensity of high expression group and low expression group was 0.007±0.005 and 0.002±0.001,respectively(P<0.001).There were certain differences in lactate dehydrogenase(LDH),C-reactive protein(CRP) and ISS staging between high expression group and low expression group(P<0.001),while no significant differences in other indicators.The overall response rate(ORR)of high expression group was significantly lower than that of low expression group(P<0.001).The median survival time of patients in high expression group was significantly shorter than that in low expression group(P=0.024).The results of bioinformatics analysis showed that the event-free survival(EFS) rate and overall survival(OS) rate of low NAMPT group were both higher than high NAMPT group(P=0.037,P=0.009),and NAMPT was an independent prognostic factor for EFS and OS(P=0.006,P=0.020).GSEA suggested that NAMPT might affect MM cell function through mTORC1signaling pathway.Conclusions:The expression level of NAMPT in bone marrow of NDMM patients is significantly higher than that of IDA patients,and the high expression of NAMPT may be correlated with late ISS stage,and high level of LDH and CRP.Patients with high expression of NAMPT have worse response to bortezomib and survival time may be shorter.NAMPT may be involved in the occurrence and development of MM through mTORC1 signaling pathway.