Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Lung Cancer A Systematic Review with Meta-Analysis

Background: Vascular endothelial growth factor (VEGF) has been implicated in tumorigenesis and metastasis, and it presumably mediates the proliferation of endothelial cells and promotes vascular permeability. However, the prognostic value of VEGF overexpression in patients with lung cancer remains controversial. Methods: Survival data from published studies were aggregated following a methodological assessment. A systematic review of eligible studies with meta-analysis was performed to quantitatively review the correlation of VEGF overexpression with survival in patients with lung cancer. Results: We conducted a final analysis of 5386 patients from 51 studies. The studies were categorized by histology, disease stage, patient race, VEGF isoform, and laboratory techniques used. Combined hazard ratios suggested that VEGF overexpression had an unfavorable impact on survival of patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). However, VEGFC and vascular endothelial growth factor receptor 3 (VEGFR3)/flt-1 overexpression did not significantly correlate with survival in patients with NSCLC. In stage I-III NSCLC with VEGF, the hazard ratio (95% confidence interval) was 1.46 (1.38-1.54) overall, 1.35 (1.24-1.46) in Asian patients, 1.61 (1.49-1.73) in non-Asian patients, 1.41 (1.17-1.65) in SCLC, 1.27 (1.06-1.47) in adenocarcinoma, 1.57 (1.43-1.70) in stage I NSCLC, 1.46 (1.38-1.55) in NSCLC by immunohistochemistry, 1.52 (1.23-1.81) in NSCLC by reverse transcription-polymerase chain reaction, 1.22 (0.96-1.47) in NSCLC with VEGFC, and 1.58 (0.96-2.20) in NSCLC with VEGFR3/flt-1. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas. Conclusion: VEGF overexpression indicates a poor prognosis for patients with NSCLC and SCLC; VEGFC and VEGFR3/flt-1 overexpression was not significantly correlated with survival for patients with NSCLC.