Preoperative plasma vascular endothelial growth factor but not nitrite is a useful complementary tumor marker in patients with colorectal cancer

PURPOSE: Vascular endothelial growth factor and nitric oxide are both related to tumor progression. This study was designed to measure preoperative plasma vascular endothelial growth factor and nitrite levels in patients with colorectal cancer to evaluate their clinical applications as tumor markers. METHODS: In total, 279 patients with primary colorectal cancer and 20 patients with hemorrhoids (as a control) were included in this study. Plasma vascular endothelial growth factor was measured by quantitative, solid-phase, enzyme-linked immunosorbent assay (R&D Systems), whereas nitrite was measured by a high-performance liquid chromatographic method. RESULTS: The vascular endothelial growth factor (mean, 220.6 pg/ml, P < 0.005) and nitrite (mean, 29.4 μM, P = 0.043) levels of patients with cancer were significantly higher than those of controls (mean vascular endothelial growth factor, 67 pg/ml; mean nitrite, 23 μM). Preoperative plasma vascular endothelial growth factor levels were positively correlated with tumor stage, T class, M class, and tumor size (Spearman correlation, P < 0.01), but were not associated with gender, N class, tumor location, histology type, or grade. There were no statistical differences in nitrite levels among different groups of patients with cancer. Higher vascular endothelial growth factor levels also were correlated with leukocytosis, elevated carcinoembryonic antigen, and a higher platelet count. The positive rates of vascular endothelial growth factor elevation (>148.6 pg/ml) compared with carcinoembryonic antigen elevation were 36.9 to 14.6 percent in Stage I, 60.9 to 33 percent in Stage II, 62.9 to 48.7 percent in Stage III, and 86 to 70.2 percent in Stage IV, respectively. The overall positive rate of vascular endothelial growth factor elevation also was higher than that of carcinoembryonic antigen elevation (63 percent for vascular endothelial growth factor vs. 42.5 percent for carcinoembryonic antigen, P = 0.016). More than one-half of the patients without carcinoembryonic antigen elevation still had elevated vascular endothelial growth factor levels. The combined assessment using vascular endothelial growth factor and carcinoembryonic antigen was superior to individual assessment using vascular endothelial growth factor or carcinoembryonic antigen. In node-negative tumor, the patients with vascular endothelial growth factor elevation had worse disease-free survival than those without vascular endothelial growth factor elevation (P = 0.0367). There was no association of vascular endothelial growth factor elevation with survival in patients with node-positive tumor. CONCLUSIONS: Plasma vascular endothelial growth factor is a useful complementary tumor marker; however, synchronous measurement of white blood cells, platelets, and carcinoembryonic antigen is suggested in the clinical application of vascular endothelial growth factor to colorectal cancer.