Ang-1在多发性骨髓瘤患者中的表达及临床意义

目的 研究血管生成素-1(angiopoietin-1,Ang-1)及其受体Tie-2在多发性骨髓瘤(MM)患者和骨髓瘤细胞株RPMI8226的表达情况,探讨其意义.方法 采用RT-PCR和Western blot方法检测112例MM患者、24例非肿瘤患者(对照组)以及RPMI8226细胞株中Ang-1及其受体Tie-2的表达水平,分析阳性率及表达水平在MM患者与对照组、MM不同分期间的差异,探讨Ang-1表达与MM患者骨髓微血管密度、临床分期及预后的关系.结果 MM组Ang-1表达阳性率、表达水平均显著高于对照组(P＜0.05);Ang-1表达阳性率在初治组和复发/难治MM组的差异无统计学意义(P＞0.05),但复发/难治MM组的Ang-1表达水平高于初治组(P＜0.05);Tie-2 mRNA仅在12例MM患者中检出,对照组未检出.MM患者骨髓微血管密度(25.21±0.80)明显高于对照组(5.23±0.20)(P＜0.01);Ang-1阳性患者的骨髓微血管密度(32.98±1.70)高于Ang-1阴性患者(16.55±1.30)(P＜0.05);Ang-1表达阳性率在Ⅱ期和Ⅲ期MM患者中差异无统计学意义(52.1%对60.9%,P＞0.05),但Ⅲ期MM患者Ang-1蛋白的表达水平(0.40±0.07)明显高于Ⅱ期患者(0.22±0.04)(P＜0.05);初治患者中,治疗无效组Ang-1表达阳性率(70.0%)明显高于有效组(19.1%)(P＜0.01).结论 Ang-1在MM患者中高表达;Ang-1表达与MM临床分期、预后判断及靶向治疗有关.

Expression and clinical significance of angiopoietin-1 in multiple myeloma

Objective To study the expression of angiopoietin-1(Ang-1)and its receptor Tie-2 in multiple myeloma(MM)patients and RPMI8226 cells,and analyze the significance of Ang-1 expression and its relevance to the tumorigenes and development of MM.Methods RT-PCR and Western blot were used to detect the expression of Ang-1 and Tie-2 in bone marrow(BM)samples from 112 MM patients and 24 control subjects,and in RPMI8226 cells.The expression levels of Ang-1 in different groups and disease stages were analyzed.Results The positive rate and expression level of Ang-1 were significantly higher in MM group than in control group(P ＜0.05).The positive rates of Ang-1 were not significantly different between newly diagnosed and relapsed/refractory MM groups,but its expression level was significantly higher in the latter group than in the former group(P ＜0.05).Tie-2 was detected only in 12 MM patients and did not in control group and RPMI8226 cells.Microvessel density in BM samples were significantly higher in MM group than in control group(25.21±0.80 vs 5.23±0.20,P＜0.01),and were higher in Ang-1-positive MM group than in Ang-1-negative M M group(32.98 ± 1.70 vs 16.55 ± 1.30,P ＜ 0.05).The positive rates of Ang-1 protein were not significantly different between stage Ⅱ and stage Ⅲ MM(52.1% vs 60.9%,P＞0.05),but the expression level of Ang-1 protein was higher in stage Ⅲ than that in stage Ⅱ MM(0.40 ±0.07 vs 0.22 ±0.04,P ＜0.05).In the newly diagnosed MM patients,the positive rate of Ang-1 protein in PD patients was significantly higher than in PR and MR patients(70.0% vs 19.1%,P ＜0.01).Conclusion High expression of Ang-1 is found in MM patients and RPMI8226 cells,and its expression is associated with the disease stage,prognosis and targeted therapy of MM.