VEGF mRNA、KDR mRNA及蛋白在非小细胞肺癌中表达的意义探讨

目的探讨非小细胞肺癌中血管内皮生长因子(VEGF)、受体KDRmRNA和蛋白表达的意义。方法应用原位杂交技术及免疫组织化学PV-9000法分别检测30例新鲜非小细胞肺癌标本中VEGFmRNA、KDRmRNA及蛋白的表达。结果VEGF、KDRmRNA和蛋白均主要分布在肺癌细胞、血管内皮细胞及纤维母细胞,肺癌细胞VEGFmRNA和蛋白的阳性率分别为66.67%(20/30)和60.00%(18/30),两者的表达有极显著正相关性(r=0.86,P<0.01);KDRmRNA和蛋白的阳性率分别为73.33%(22/30)和76.67%(23/30),两者的表达亦有极显著正相关性(r=0.7366,P<0.01);VEGFmRNA、KDRmRNA及相应蛋白在肺癌细胞中的表达均呈极显著性正相关(原位杂交r=0.853,免疫组化r=0.5148,均P<0.01);肺癌细胞VEGFmRNA、KDRmRNA及相应蛋白的阳性表达率在不同大小的3组肺癌标本间,差异均具有显著性(确切P=0.014,P=0.002;P=0.0087,P=0.0016);淋巴结有转移组的VEGFmRNA、KDRmRNA及相应蛋白在肿瘤细胞中的阳性表达率显著高于淋巴结无转移组者(确切P=0.007,P=0.003;P=0.0008,P=0.0073)。结论肺癌细胞产生的VEGF通过自分泌环作用于癌细胞上的KDR受体促进癌细胞生长;VEGF及KDR的检测可作为肺癌淋巴结转移的有效评估指标;VEGF及KDR有望成为肺癌治疗的新靶点。

Significance of expression of VEGF mRNA, KDR mRNA and corresponding proteins in non-small cell lung cancer

[Objective] To investigate the significance of expression of vascular endothelial growth factor (VEGF), KDR mRNA and corresponding proteins in non-small cell lung cancer. [Methods] The expression of mRNA and protein of VEGF, KDR was examined in 30 cases fresh non-small cell lung cancer (NSCLC) by in situ hybridization (ISH) and immunohistochemistry (IHC) differently. [Results] VEGF mRNA, KDR mRNA and corresponding proteins were all mainly in the cytoplasm of tumor cells (TCs), fibroblasts (FBs), endothelial cells (ECs). The positive rate of VEGF mRNA and corresponding protein in TC was 66.67% (20/30), 60.00% (18/30), and it of KDR mRNA, its protein was 73.33% (22/30), 76.67% (23/30). There were positive correlations both between mRNA and corresponding protein in TC (r=0.86, 0.7366; P <0.01). There were also significantly positive correlations both between the positive rate of VEGF and KDR in TC detected by ISH and IHC (r=0.853,0.5148; P <0.01), respectively. It was obviously all different that the positive rate of VEGF, KDR mRNA and proteins in TC among the three groups with varying tumor diameter (P =0.014, P =0.002; P =0.0087, P =0.0016). The expression of VEGF, KDR mRNA and proteins in TC with lymph node metastasis was higher than that without lymph node metastasis (P =0.007,P =0.003;P = 0.0008, P =0.0073). [Conclusion] VEGF may promote the growth of TC, mainly in an autocrine manner via KDR. Detecting the expression of VEGF and KDR may be more valuable for evaluating lymph node metastasis of NSCLC patients. VEGF and KDR will be new targets for lung cancer treatment.