SMAD4 and cancer: The high level of VEGF activation was significantly associated with advanced tumor stage and lymphatic metastasis, which subsequently involved the alterations of a series of genes, including some oncogenes and tumor suppressor genes, such as K-ras, c-myc, c-fos, c-erbB-2, p53, p16 and deleted in pancreatic cancer, locus 4 (DPC4).