SMAD4 and pancreatic neoplasm: Approximately 55% of pancreatic cancer patients have loss or downregulation of SMAD4, which is considered a key factor in the malignant progression of pancreatic cancer.21 Research involving sequencing for SMAD4 gene mutations and homozygous deletions has revealed genetic abnormalities in pancreatic cancer, with SMAD4 mutations being prevalent in a large number of cases.22 In addition, studies have shown that the inactivation of the SMAD4 gene is associated with poorer prognosis in patients who have undergone surgical resection of pancreatic cancer.23,24