Expression and clinical significances of adhesion molecules in patients with newly diagnosed multiple myeloma

Abstract

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 Key words: Multiple myeloma; Vascular cell adhesion molecule-1; Cell adhesion molecules; Selectins