Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be ...Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer(NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry(IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor(KDR) and NRP-1 copy number gain(CNG) was assessed by fluorescence in situ hybridization(FISH). The distributions of overall survival(OS) and progression-free survival(PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG(+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue(χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs(χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status(P〈0.05), but not age, gender or pathology type(P〉0.05). VEGFR2 showed a strong correlation with NRP-1(Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG(Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression(P〈0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis(P〈0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC.展开更多
基金supported by National Natural Science Foundation of China [81472792]Ministry of Health of China (W201210)Jiangsu Natural Science Foundation of China (BK2012661)
文摘Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer(NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry(IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor(KDR) and NRP-1 copy number gain(CNG) was assessed by fluorescence in situ hybridization(FISH). The distributions of overall survival(OS) and progression-free survival(PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG(+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue(χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs(χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status(P〈0.05), but not age, gender or pathology type(P〉0.05). VEGFR2 showed a strong correlation with NRP-1(Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG(Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression(P〈0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis(P〈0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC.