In addition, the elevated serum VEGF-C was positively correlated with decreased OS and increased lymph node metastasis.95,96 In a large cohort study with 195 GBC patients and 300 healthy serum samples, polymorphisms of c.*237C > T and g.43737830A > G of VEGF gene were associated with the disease development, indicating that VEGF polymorphisms may offer a valuable marker to predict the susceptibility of carcinogenesis.97 In line with clinic trials, blocking VEGF-C by short interfering RNA or a neutralizing antibody in cultured GBC cells inhibited tumor cell proliferation and invasion. This evidence concerns the gene VEGFA and metastatic malignant neoplasm in the lymph nodes.