Serum vascular endothelial growth factor-C and lymphoangiogenesis are associated with the lymph node metastasis and prognosis of patients with colorectal cancer

Abstract

The study aims to investigate the relationship among serum vascular endothelial growth factor (SVEGF-C), VEGF-C expression and lymph vessel density (LVD) in tumour tissue, and their influence to colorectal carcinoma (CRC). The SVEGF-C concentration of 110 patients with CRC and 40 healthy donors was examined by ELISA. The 110 tumour tissues and 40 normal colorectal specimens were examined by immunohistochemical staining (SP method) with VEGF-C and podoplanin (lymphatic vessel specific antibody). Kaplan–Meier survival analysis determined the influence on CRC prognosis. CRC SVEGF-C level (889.0 ± 264.0 pg/mL) significantly exceeded (P = 0.000) the control level (373.2 ± 97.3 ng/L), and was significantly higher in T3, lymph node metastasis (LNM), distant metastasis, and pTNM groups III and IV. LNM prediction sensitivity, specificity, and accuracy of SVEGF-C were 85.7, 80.0 and 83.6%, respectively (875 pg/mL cut-off). VEGF-C expression was elevated in CRC versus control patients (P = 0.000), and was significantly related to LNM and pTNM stages III and IV. Mean LVD in CRC (6.3 ± 0.7/200 HP) significantly exceeded control mean (3.0 ± 0.7/200 HP) (P = 0.000). LVD was significantly higher in LNM and pTNM stages III and IV. SVEGF-C level was significantly higher in VEGF-C positive versus negative patients (P = 0.000), and was related to LVD (P = 0.009). Kaplan–Meier ranking of prognostic factors was SVEGF-C level (P = 0.000), VEGF-C expression (P = 0.001) and LVD (P = 0.012). SVEGF-C level, VEGF-C and LVD are related to LNM and poor prognosis in patients with CRC. SVEGF-C may be a biomarker for LNM in CRC.