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The transcription factor Stat1 is a member of the family of signal transducers and transcription activators and responds to interferon-γ stimulation. p21 is a p53-responsive gene for cell cycle regulation and mediates Stat1 antitumor activity. The aim of this study was to analyze their expression for prediction of pancreatic cancer progression and prognosis.A total of 100 pancreatic adenocarcinoma tissue specimens were used for construction of a pancreatic cancer tissue microarray for immunohistochemical staining of Stat1 and p21 expression.Stat1 and p21 proteins were expressed in 88% (88/100) and 82% (82/100) of pancreatic adenocarcinoma tissue specimens, and the expression was inversely associated with tumor differentiation, clinical stages, and lymph node metastasis of pancreatic cancer. There was no association with age, tumor size, or invasion. Moreover, the Kaplan-Meier curve analysis showed that patients with higher Stat1 and p21 expression had better overall survival rates than those with low expression of Stat1 and p21 proteins.The loss of expression of Stat1 and p21 proteins corresponded to lymph node metastasis, advanced stage, tumor dedifferentiation, and poor prognosis in patients with pancreatic cancer.