VEGF及其受体在多发性骨髓瘤中的表达及意义

Expression and Clinical Significance of Vascular Endothelial Growth Factor and Its Receptors in Multiple Myeloma

背景与目的:骨髓新生血管形成在多发性骨髓瘤(multiple myeloma,MM)的发生、发展和预后中起着重要的作用,血管内皮生长因子(vascular endothelial growth factor,VEGF)在此过程中扮演了关键角色。本研究旨在研究VEGF及其受体在MM中的表达,分析其与MM发生、发展的关系。方法:采用RT-PCR的方法检测35例MM患者、16例非肿瘤患者(下称对照组)以及KM3细胞株中VEGF及其受体Flt-1和KDR的表达,并分析阳性率以及表达相对含量在MM患者和非肿瘤患者、MM不同分期间的差异。结果:VEGF和Flt-1基因在MM组的阳性率(62.9%和80.0%)显著高于对照组(18.8%和31.3%)(P<0.01),VEGF在两组中的表达水平为0.41±0.19vs.0.06±0.01(P<0.05),Flt-1为0.60±0.33vs.0.08±0.03(P<0.01);VEGF基因在初治组和复发/难治MM组的阳性率为66.7%vs.60.9%(P>0.05),Flt-1基因为83.3%vs.78.3%(P>0.05);VEGF在Ⅱ期和Ⅲ期MM的阳性率为50%vs.73.7%(P>0.05),Flt-1为81.3%vs.78.9%(P>0.05);复发/难治MM组的VEGF和Flt-1基因的表达水平明显高于初治组(0.49±0.20vs.0.28±0.04,P<0.05;0.70±0.38vs.0.41±0.06,P<0.05),Ⅲ期MM患者VEGF和Flt-1基因的表达水平明显高于Ⅱ期患者(0.48±0.19vs.0.28±0.09,P<0.05;0.75±0.35vs.0.41±0.21,P<0.05)。KDR仅在3例MM患者中检出,对照组未检出。结论:VEGF和Flt-1在MM中高表达,并与疾病进展相关。

BACKGROUND ＆ OBJECTIVE： Bone marrow angiogenesis plays an important role in the development and prognosis of multiple myeloma （MM）. Vascular endothelial growth factor （VEGF） is the most potent stimulatory factor in angiogenesis. This study was to examine the expression of VEGF and its receptors in MM, and analyze their correlations to the tumorigenesis and development of MM. METHODS： Reverse transcription-polymerase chain reaction （RT-PCR） was used to detect mRNA expression of VEGF, Fit-l, and KDR in bone marrow samples from 12 newly diagnosed MM patients, 23 relapsed/refractory MM patients, 16 control people, and in KM3 cells. RESULTS： The positive rates of VEGF and Fit-1 were significantly higher in MM patients than in control people （62.9% vs. 18.8%, P〈0.01;80% vs. 31.3%, P〈0.01）. The mRNA levels of VEGF and Fit-1 were significantly higher in MM patients than in control people （0.41±0.19 vs. 0.06±0.01 ,P〈0.05; 0.60±0.33 vs.0.08±0.03, P〈0.01）. The positive rates of VEGF and Fit-1 mRNA were not significantly different between newly diagnosed and relapsed/refractory MM patients （66.7% vs. 60.9%, P〉0.05; 83.3% vs. 78.3%, P〉0.05）, and between stage Ⅱ MM and stage Ⅲ MM （50% vs. 73.7%, P〉0.05; 81.3% vs. 78.9%, P〉0.05）. The mRNA levels of VEGF and Fit-1 were significantly higher in relapsed/refractory MM patients than in newly diagnosed MM patients （0.49±0.20 vs. 0.28±0.04, P〈0.05; 0.70±0.38 vs. 0.41±0.06, P〈0.05）, and were significantly higher in stage Ⅲ MM than that in stage Ⅱ MM （0.48＋0.19 vs. 0.28＋0.09, P〈0.05; 0.75＋0.35 vs. 0.41＋0.21, P〈0.05）. KDR was detected only in 3 MM patients and was not detected in control group. CONCLUSION. High expression of VEGF and Fit-1 mRNA is associated with the development of MM.