血管内皮细胞生长因子与穿膜蛋白在骨肉瘤中的表达及相关性研究

A study on the expressions of vascular endothelial growth factor and delta like 1 homolog in osteosarcoma and their association

目的研究血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)与穿膜蛋白(delta like 1 homolog,DLK1)在骨肉瘤中的表达,并探讨二者的表达与骨肉瘤分级、转移和预后的关系及其二者的相关性,为骨肉瘤侵袭和转移调控机制的研究打基础。方法应用微波链霉菌抗生物素蛋白-过氧化物酶连结(streptavidin perosidase,SP)免疫组化法检测42例骨肉瘤患者(实验组)组织中的VEGF和DLK1的表达水平,同时设30例良性的骨软骨瘤作为阴性对照组。结合骨肉瘤的生物学行为及临床随访资料对VEGF和DLK1的表达与骨肉瘤分级、转移和预后的相关性及骨肉瘤细胞中VEGF和DLK1表达的相关性进行分析。结果骨肉瘤中VEGF和DLK1的阳性表达率分别是76.2%和66.7%,骨软骨瘤中VEGF和DLK1的阳性表达率都为0,且骨肉瘤中VEGF和DLK1的阳性表达率显著高于对照组(P<0.05)。VEGF在不同病理分级(高、中、低分化)及Enneking分期(I^II A期、II B^III期)骨肉瘤组织中的阳性表达不同,差异有统计学意义(P<0.05),且随着病理分级和Enneking外科分期的升高,VEGF的阳性表达率也呈增强趋势;DLK1在不同病理分级的骨肉瘤组织中的阳性表达不同,差异有统计学意义(P<0.05),且随着病理分级的升高,DLK1阳性表达强度也随之增强。VEGF与DLK1有相关性,二者呈正相关(r=0.8957,P<0.05)。VEGF、DLK1的表达与骨肉瘤转移均呈显著正相关性(r=0.6782、r=0.7643,P<0.05)。VEGF、DLK1的表达与骨肉瘤预后呈显著正相关性(r=0.8462、r=0.8758,P<0.05)。结论 VEGF与DLK1在骨肉瘤细胞中均高度表达;VEGF和DLK1表达阳性者骨肉瘤患者的肿瘤恶性程度高、转移率高、预后差;VEGF和DLK1表达阳性是骨肉瘤的分级、转移和预后不良的重要生物学指标,二者在骨肉瘤的发生和转移上可能具有相互协同作用。

Objective To study the relationship between the expressions of vascular endothelial growth factor （ VEGF ） and delta like 1 homolog （ DLK1 ） and the grade, metastasis and prognosis of osteosarcoma, and to lay a foundation for the research on invasion and metastasis mechanism of osteosarcoma.Methods The expressions of VEGF and DLK1 in 42 patients with osteosarcomas were detected using microwave Streptavidin-Perosidase （ SP ） immunohistochemical method, who were taken as the experimental group. In the negative control group, there were 30 patients with benign osteochondromas. Based on the biological behavior of osteosarcoma and clinical follow-up data, the relationship between the expressions of VEGF and DLK1 and the grade, metastasis and prognosis of osteosarcoma and the correlation between the expressions of VEGF and DLK1 in osteosarcoma cells were analyzed. Results In osteosarcoma cells, the expression rates of VEGF and DLK1 were 76.2% and 66.7%. In osteochondroma cells, the expression rates of VEGF and DLK1 were 0 and 0. The positive expression rates of VEGF and DLK1 in osteosarcoma cells were signiifcantly higher than that in osteochondroma cells （P〈0.05 ）. According to pathological grading and Enneking staging, statistically signiifcant differences existed in the positive expression rate of VEGF in osteosarcoma cells at different grades （ high, medium and low ） and stages （ I-II A and II B-III ） （P〈0.05 ）. With the increase of pathological grade and Enneking stage, the positive expression rate of VEGF became higher and higher. Differences existed in the positive expression rate of DLK1 in osteosarcoma cells at different pathological grades,which were statistically signiifcant （P〈0.05 ）. With the increase of pathological grade, the positive expression rate of DLK1 became higher and higher. There was a positive correlation between the expressions of VEGF and DLK1 （r=0.8957,P〈0.05 ）. A significant positive correlation existed between the expressions of VEGF and DLK1 and metastasis of osteosarcoma （r=0.6782,r=0.7643,P〈0.05 ）. And a significant positive correlation was also found between the expressions of VEGF and DLK1 and prognosis of osteosarcoma （r=0.8462,r=0.8758,P〈0.05 ）. Conclusions VEGF and DLK1 are highly expressed in osteosarcoma. If the positive expression rates of VEGF and DLK1 are high in osteosarcoma, the malignancy and metastasis rate are high and the prognosis is poor. The positive expression rates of VEGF and DLK1 act as important biological indicators for the grade, metastasis and poor prognosis of osteosarcoma, which may also work in coordination with each other in the proliferation and metastasis of osteosarcoma.