AIM To detect the expression of pleiotrophin(PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion(PNI).METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis.RESULTS The expression rates of PTN and N-syndecan proteinswere 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI(P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites(P = 0.009), liver metastasis(P = 0.035), and decreased survival time(P = 0.022). N-syndecan expression was significantly associated with tumor size(P = 0.025), but not with survival time(P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer. AIM To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 days. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. rates of PTN and N-syndecan proteinwere 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression were associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large (P = 0.025), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but n ot with survival time (P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.