SMAD4 and familial pancreatic carcinoma: Multivariate analysis based on pancreatic cancer patients showed that low-level Smad7 and Smad4 expression had shown a significant negative correlation with lymph node metastasis [44, 45], while TGF-beta, playing a distinct role in PDAC pathogenesis, can mediate tumor promotion or a more aggressive phenotype attributing its effect on tumor cell and tumor-supportive microenvironment.