Two recent meta-analyses reported that a loss of SMAD4 expression in PC was significantly correlated with an inferior overall survival (OS) (hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.03–1.40 and HR 0.61, 95% CI 0.38–0.99, respectively) and that the frequency of SMAD4 protein loss was significantly increased in pancreatic ductal adenocarcinoma than in nonmalignant pancreatic tissue, making it also a potential diagnostic marker for PC [13,14]. This evidence concerns the gene SMAD4 and pachyonychia congenita.