title: Expression of VEGFR2 and NRP-1 in non-small cell lung cancer and their clinical significance.
abstract: 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 (χ(2)=11.22, P=0.001; χ(2)=9.82, P=0.001, respectively); similar results were obtained using CNGs (χ(2)=4.39, P=0.036; χ(2)=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 anti-angiogenic treatment in NSCLC.
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Ding
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Chengxi
authors.initials: C
authors.lastname: Hu
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: 1 Xuzhou Medical College, Xuzhou 221006, China ; 2 Department of Oncology, Xuzhou Cancer Hospital, Xuzhou 221005, China ; 3 Department of Radiotherapy Oncology, Lianyungang First People's Hospital, Lianyungang 222002, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
keywords: Non-small cell lung cancer (NSCLC); fluorescence in situ hybridization (FISH); neuropilin-1 (NRP-1); vascular endothelial growth factor receptor 2 (VEGFR2)