摘要：
Objective To investigate the expression and clinical significances of adhesion molecules in patients with newly diagnosed multiple myeloma (NDMM).Methods From January 2009 to January 2012,a total of 145 patients with NDMM who were treated in Yulin First Hospital of Shaanxi Province were enrolled in the NDMM group (n =145).Among them,there were 33 patients with International Staging System (ISS)-Ⅰ,45 patients with ISS-Ⅱ and 67 patients with ISS-Ⅲ.There were 61 patients with asymptomatic / smokeless myeloma (SMM) and 47 patients with unexplained monoclonal gamma globulin disease (MGUS) who were selected as SMM group (n=61) and MGUS group (n=47),respectively.The levels of vascular cell adhesion molecules (VCAM)-1,intercellular adhesion molecule (ICAM)-1,P-,L-and E-selectin and characteristics of NDMM(β2-microglobulin,creatinine,urea and albumin levels) were detected in NDMM group,respectively,SMM group and MGUS group.The levels of adhesion molecules were compared among three groups and among differents ISS stages.The relationship between adhesion molecule levels and characteristics of NDMM in the NDMM group were analyzed.The overall survival (OS) of NDMM patients were followed up,meanwhle the influencing factors of OS in NDMM patients were analyzed by univariate Cox regression analysis.Multivariate Cox regression analysis was used to analyze the independent risk factors of OS in patients with NDMM based on the results of existing studies,clinical experiences and results of univariate Cox regression analysis.Results ①The level of VCAM-1 in NDMM group was significantly higher than those of SMM group and MGUS group,and the differences were statistically significant (Z=4.33,2.71;P=0.001,0.009).There was significant difference between SMM group and MGAM group in the level of VCAM-1 (Z=1.79,P=0.047).The levels of ICAM-1 in NDMM group and SMM group were significantly higher than that of MGUS group (Z =2.70,2.97;P =0.009,0.007).There was no significant difference in ICAM-1 level between NDMM group and SMM group (Z=0.18,P=0.870).The levels of L-and P-selectin in NDMM group were significantly lower than those of SMM group and MGUS group,respectively,and the differences were statistically significant (L-selectin level:Z=3.77,9.86,P-0.002,0.001;P-selectin level:Z=6.71,8.48,P =0.001,0.001).There were no significant differences in levels of L-and P-selectin between SMM group and MGUS group (Z=1.01,0.31;P =0.640,0.780).There were no significant differences in E-selectin level among three groups (P＞0.05).②The level of VCAM-1 of patients with ISS-Ⅰ was significantly lower than that of patients with ISS-Ⅱ and ISS-Ⅲ in NDMM group,respectively,and the differences were statistically significant (Z=2.91,8.72;P=0.007,0.001).The level of P-selectin in ISS-Ⅰ patients was significantly higher than those of ISS-Ⅱ and ISS-Ⅲ patients in NDMM group,respectively,and the differences were also statistically significant (Z=2.66,3.47;P =0.013,0.002).There were no significant differences in the levels of ICAM-1,L-and E-selectin in NDMM patients with different ISS stages (P＞0.05).③There was a positive correlation between ICAM-1 and VCAM-1 levels in patients with NDMM (r=0.466,P=0.001),and the ICAM-1 level was negatively correlated with P-selectin level (r=-0.216,P=0.011).There was a positive correlation between VCAM-1 level and β2-microglobulin,urea and creatinine levels in NDMM group (r=0.560,0.430,0.436;P=0.002,0.001,0.001),and the VCAM-1 level was negatively correlated with albumin levels (r=-0.167,P =0.018).P-and L-selectin levels were negatively correlated with β2-microglobulin,creatinine and urea levels (P-selectin level:r=-0.430,-0.215,-0.339,P =0.006,0.021,0.017;L-selectin level:r=-0.284,-0.321,-0.251,P=0.033,0.002,0.001),and P-and L-selectin levels had positive correlations with albumin levels (r=0.354,0.381;P =0.001,0.001).④The univariate Cox regression analysis showed that VCAM-1 level (HR =0.546,95％ CI:0.376-0.981,P =0.003),P-selectin level(HR =0.490,95 ％ CI:0.277-0.998,P =0.017),ISS stage (HR =0.476,95 ％ CI:0.341-0.965,P=0.026) and lactate dehydrogenase (LDH) level (HR=0.466,95％CI:0.272 0.873,P=0.001) were influencing factors of OS in NDMM patients.Multivariate Cox regression analysis showed that VCAM-1 level ≥799 ng/mL(HR=0.444,95％CI:0.246-0.801,P-0.007),LDH level ＜300 U/L(HR=0.350,95％CI:0.133-0.919,P=0.033) and ISS stage (HR-0.392,95％％CI:0.225-0.681,P=0.001) were independent risk factors of OS in NDMM patients.Conclusions VCAM-1 level is an independent risk factor for OS in patients with NDMM.However,whether VACM-1 can be used as a potential target for anti-NDMM treatment,still need further study to confirm%目的 探讨新诊断多发性骨髓瘤(NDMM)患者黏附分子的表达及其临床意义.方法 选择2009年1月至2012年1月,于陕西省榆林市第一医院治疗的145例NDMM患者为研究对象,纳入NDMM组(n=145),其中,国际分期体系(ISS)分期系ISS-Ⅰ期患者为33例,ISS-Ⅱ期患者为45例,ISS-Ⅲ期患者为67例.选择61例无症状/冒烟型骨髓瘤(SMM)患者与47例意义未明单克隆免疫球蛋白病(MGUS)患者作为对照,将其分别纳入SMM组(n=61)和MGUS组(n=47).观察NDMM组、SMM组及MGUS组患者血管细胞黏附分子(VCAM)-1,细胞间黏附分子(ICAM)-1及P-、L-、E-选择素等黏附分子水平,以及NDMM组患者的疾病特征(β2-微球蛋白、肌酐、尿素和白蛋白水平).统计学比较3组患者黏附分子水平,NDMM组不同ISS分期患者的黏附分子水平,以及分析NDMM组患者黏附分子水平与MM疾病特征的相关性.观察NDMM组患者总体生存(OS)期,采用单因素Cox回归分析方法,分析NDMM患者OS期的影响因素.根据已有研究结果、临床经验及单因素Cox回归分析中差异有统计学意义的影响因素,采用多因素Cox回归分析,对NDMM患者OS期的独立危险因素进行分析.结果 ①NDMM组VCAM-1水平,显著高于SMM组与MGUS组,并且差异均有统计学意义(Z=4.33、2.71,P=0.001、0.009).SMM组与MGUS组VCAM-1水平比较,差异亦有统计学意义(Z=1.79,P=0.047).NDMM组与SMM组ICAM-1水平,均显著高于MGUS组,并且差异均有统计学意义(Z=2.70、2.97,P=0.009、0.007).NDMM组和SMM组ICAM-1水平比较,差异无统计学意义(Z=0.18,P=0.870).NDMM组L-、P-选择素水平,均显著低于SMM组和MGUS组,并且差异均有统计学意义(L-选择素水平:Z=3.77、9.86,P=0.002、0.001;P-选择素水平:Z=6.71、8.48,P=0.001、0.001).SMM组与MGUS组的L-、P-选择素水平分别比较,差异均无统计学意义(Z=1.01、0.31,P=0.640、0.780).3组E-选择素水平分别比较,差异均无统计学意义(P＞0.05).②NDMM组ISS-Ⅰ期患者的VCAM-1水平,显著低于ISS-Ⅱ、-Ⅲ期患者,并且差异有统计学意义(Z=2.91、8.72,P=0.007、0.001).NDMM组ISS-Ⅰ期患者的P-选择素水平,显著高于ISS-Ⅱ、-Ⅲ期,并且差异亦有统计学意义(Z=2.66、3.47,P=0.013、0.002).NDMM组不同ISS分期患者的ICAM-1及L、E-选择素水平分别比较,差异均无统计学意义(P＞0.05).③NDMM组患者ICAM-1水平与VCAM-1水平呈正相关关系(r=0.466,P=0.001),与P-选择素水平呈负相关关系(r=-0.216,P=0.011).NDMM组患者VCAM 1水平与β2-微球蛋白、尿素和肌酐水平均呈正相关关系(r=0.560、0.430、0.436,P=0.002、0.001、0.001),与白蛋白水平呈负相关关系(r=-0.167,P=0.018).P-、L-选择素水平与β2-微球蛋白、肌酐和尿素水平均呈负相关关系(P-选择素水平:r=-0.430、-0.215、-0.339,P=0.006、0.021、0.017;L-选择素水平:r=-0.284、-0.321、-0.251,P=0.033、0.002、0.001),与白蛋白水平呈正相关关系(r=0.354、0.381,P=0.001、0.001).④NDMM患者OS期影响因素的单因素Cox回归分析结果显示,VCAM-1水平(HR=0.546,95％CI:0.376～0.981,P=0.003),P-选择素水平(HR=0.490,95％CI:0.277～0.998,P=0.017),ISS分期(HR=0.476,95％CI:0.341～0.965,P=0.026)及乳酸脱氢酶(LDH)水平(HR=0.466,95％CI:0.272～0.873,P=0.001),均为NDMM患者OS期的影响因素.NDMM患者OS期影响因素的多因素Cox回归分析结果显示,VCAM-1水平≥799 ng/mL(HR=0.444,95％CI:0.246～0.801,P=0.007),LDH水平＜300 U/L(HR=0.350,95％CI:0.133～0.919,P=0.033)和ISS分期(HR=0.392,95％CI:0.225～0.681,P=0.001),均为NDMM组患者OS期的独立危险因素.结论 VCAM-1水平是NDMM患者OS期的独立危险因素.但是,VCAM-1是否可以作为抗NDMM治疗的潜在靶点,则尚需进一步研究、证实.
