Clinical Significance of Plasma Level of Vascular Endothelial Growth Factor-C in Patients with Colorectal Cancer

Vascular endothelial growth factor (VEGF)-C is known to be associated with angiogenesis and lymphangiogenesis in various cancers. However, little is known about the clinical significance of determining the blood level of VEGF-C in patients with colorectal cancer. Plasma levels of VEGF-C in patients with colorectal cancer (n = 127) and normal healthy volunteers (n = 23) were determined by the sandwich enzyme-linked immunosorbent assay. The plasma VEGF-C concentration did not significantly differ between patients with colorectal cancer and healthy controls (P = 0.53). However, subgroup analysis showed that deeper tumor invasion (P = 0.04), more severe lymphatic invasion (P = 0.03) and venous invasion (P < 0.01) were correlated with an elevated level of plasma VEGF-C. Among the patients (n = 109) who underwent potentially curative surgery, the plasma level of VEGF-C was higher in patients who developed recurrence (n = 35) than in those who did not (n = 74) (P = 0.04). In addition, disease-free (P = 0.02) and overall survival times (P = 0.02) were shorter in patients with a high level (> 1840 pg/ml) of plasma VEGF-C than in those with a low level (<= 1840 pg/ml) when the cut-off value was determined on the basis of the median value in colorectal cancer patients. Multivariate analysis with the Cox proportional hazard model demonstrated that the plasma VEGF-C level along with Dukes' stage was an independent factor affecting overall survival (P = 0.03). These results suggest that determining the plasma level of VEGF-C would be useful for predicting lymphatic invasion, venous invasion and poor outcome of patients with colorectal cancer.