Background: Currently, there are few effective therapeutic options for pancreatic cancer patients.Sortilin is a member of vps10p receptor family，reported in many types of cancers.However, the underlying mechanism and prognostic value of sortilin in pancreatic cancer are still unclear.
Objective:Understand the expression of sortilin in pancreatic cancer, and analyze its mechanism that affects the occurrence and development of pancreatic cancer.
Methods:A tissue microarray of 115 pancreatic cancer metastases was analyzed by immunohistochemistry. All data were analyzed by univariate analysis and multivariate analysis.Multivariate logistic regression analysis and the area under the receiver operating characteristic (ROC) curve were used to analyze the ability of sortilin in predicting pancreatic cancer.Next, survival analysis was performed to compare the survival time between high-risk and low-risk patients to validate the prognosis prediction efficacy of sortilin.The effects of sortilin on the invasion，metastasis and proliferation of pancreatic cancer cells were investigated both in vitro. investigate the anti-cancer effect of soritlin on human pancreatic cancer Capna1 and Bxpc3 cells, and its possible molecular mechanism.
Results:Differential expression analysis of 115 tissue microarrays showedsortilin expression was up‐regulated in pancreatic cancer tissues,and it mainly comes from the nucleus. Sortilin expression in nucleus(SEIN) was only negatively correlated with N stage, Binary logistic regression model showed that SEIN is a good diagnostic marker for predicting pancreatic cancer and the accuracy of prediction is as high as 79.1 %. ROC curve analysis demonstrated a statistically significant diagnostic value of SEIN,and the diagnostic accuracy was 86.3%, The Youden Index was calculated to evaluate the diagnostic power, The cut-off value for SEIN in pancreatic cancer diagnosis was 0.85, with a sensitivity of 90.9% and a specificity of 68.3%. Univariate analysis showed that M stage(P=0.022), histological grade(P=0.021), clinic stage(P=0.030)and SEIN(P=0.039) were correlated with prognosis of pancreatic cancer patients, Multivariate regression analysis showed that M stage(P=0.036)and ESIN(P=0.004) were independent factors.
The proliferation, invasion and migration of pancreatic cancer cells were inhibited in vitro by sortilin siRNA knockdown.it may have something to do with soritlin/P53/NFκB regulated the the proliferation function and sortilin/MMP9 regulated the invasion-promotion of pancreatic cancer cells.
Conclusions: These fndings demonstrated that the low expression of SEIN indicates better prognosis in pancreatic cancer and supplemented the effect mechanism of sortilin on pancreatic cancer cells. SEIN expression may serve as a potential diagnostic indicator of pancreatic cancer.