Argonaute 2与多发性骨髓瘤血管生成临床关系研究

目的 了解Argonaute 2(Ago2)在多发性骨髓瘤(MM)骨髓组织中的表达水平,探讨其与骨髓内血管生成的关系.方法 应用改良的甲基丙烯酸甲酯(MMA)单体塑料包埋法对59例MM患者及16例正常对照进行骨髓活组织检查的组织制片,采用EnVision免疫组织化学二步法检测MM患者及正常对照骨髓组织中Ago2蛋白表达水平及微血管密度(MVD),并用Western blot方法检测8例MM患者和3例正常对照Ago2蛋白表达水平.结果 Western blot检测显示,Ago2蛋白在MM患者骨髓组织中表达高于正常对照(1.35±0.19比0.15±0.03,t=-19.883,P＜0.001).免疫组织化学结果表明,59例MM患者骨髓组织中Ago2蛋白阴性和阳性分别为9例和50例,对照组16例均为阴性,两组差异有统计学意义(x2=42.586,P＜ 0.001).MM患者中,Ago2阳性组β2-微球蛋白高于阴性组,差异有统计学意义(Z=-2.014,P=0.042).MM患者骨髓组织中MVD为7.89±4.88,正常对照组为2.16±1.32,两组之间差异有统计学意义(t=4.63,P＜0.001).MM患者骨髓组织中Ago2蛋白表达水平与MVD具有相关性(r=0.461,P=0.023).Ago2蛋白阳性组MVD较阴性组增高,差异有统计学意义(t=2.71,P=0.009).结论 Ago2在MM患者骨髓组织中表达水平明显升高,可能参与了MM患者的病理发生,并对骨髓内异常新生血管生成起一定的调节作用.

Relationship between Argonaute 2 expression and angiogenesis of multiple myeloma

Objective To assess the Argonaute 2 (Ago2) expression in the bone marrow of multiple myeloma (MM) and explore its association with angiogenesis.Methods Fifty-nine MM patients and sixteen normal controls were included.The bone marrow sections were made from plastic (methyl-methacrylate)-embedded bone marrow biopsies.The expression of Ago2 and CD34 in the bone marrow sections was detected by EnVison immunohistochemistry, and the microvessel density (MVD) was assessed.The Ago2 protein expression levels in bone marrow were also determined by Western blot in 8 MM patients and 3 normal controls.The clinical significances of Ago2 expression and MVD in MM were analyzed.Results Western blot analysis indicated that the Ago2 expression was significantly increased in the bone marrow of MM patients compared with normal controls (1.35±0.19 vs.0.15±0.03, t =-19.883, P ＜ 0.001).As assessed by immunohistochemistry, fifty MM patients were positive for Ago2 and nine patients were negative.However, sixteen normal controls were all negative for Ago2 (x2 =42.586, P ＜ 0.001).The β2-microglobulin level was significantly higher in the Ago2 positive group than that in the Ago2 negative group (Z =-2.014, P =0.042).The MVD was significantly higher in bone marrow samples of MM patients than that in the normal controls (7.89±4.88 vs.2.16±1.32, t =4.63, P ＜ 0.001).Analysis of the correlation coefficients showed that Ago2 expression was positively associated with MVD in MM patients (r =0.461, P =0.023).MVD was also significantly higher in the Ago2 positive group than that in the Ago2 negative group (t =2.71, P =0.009).Conclusions It is found that Ago2 expression is significantly increased in the bone marrow of MM patients.Ago2 may participate in the pathogenesis of MM and mediate the angiogenesis.