The Relationship Between HENT1, CREPT And Chemoresistance And Prognosis Of Pancreatic Cancer

BackgroundPatients suffering from pancreatic adenocarcinoma have a poor prognosis,with annually increasing morbidity.Failing to be diagnosed in early stage,lacking of prognostic marker and chemotherapeutic resistance heavily hinder patients obtain long-term survival.So,it is important to find a marker to determine how these patients failing to derive benefit from chemotherapeutic can be identified before early relapse or metastasis.The identified of a molecular marker that can predict the effectiveness of gemcitabine-base chemotherapy would help change the current method of treatment in which patients are treated empirically until evidence of disease progression is detected.hENT1 plays a dominant role in the transport of gemcitabine across the cell membrane.It has been reported that the expression of hENT1 is realated with gemcitabine-based chemotherapeutic response.However,the basic research about the role of hENT1 gene expression in pancreatic cancer cells is not very clear.And the current clinical studies related with hENT1 have reached different results in different studies,duo to the inconfirmed standard of patients inroled in each study and the different kinds of hENT1 score medthod.This study was performed to detect the role of hENT1 in pancreatic cancer cell and to determine if a difference in hENT1 protein expression exists and whether such a difference could predict the patients’ response to gemcitabine-based chemotherapyObjectiveThis study was performed to detect the role of hENT1 in pancreatic cancer cell and to determine if a difference in hENT1 protein expression exists and whether such a difference could predict the patients’ response to gemcitabine-based chemotherapyMethodsDetect hENT1 expression level in 6 pancreatic caner cell lines.Construct hENT1 high expression and/or low expression stable cell lines.Detect the role of hENT1 in cell proliferation,,drug resistance,migration and invasion.Detect hENT1 expression through immunohistochemical method;Study the correlations between hENT1 expression and various clinicopathological factors,including survival status.ResultsIn the six pancreatic caner cell lines,the higher hENTl expression was detected in Panc-1 cell line and the lower hENT1 expression was detected in T3M4 cell line.Through up and/or slince the hENT1 gene,the hENT1 overexpression stable cell line and the hENT1 slince stable cell line were established.Up regulating hENTI can impove the chemotherapy sensitivity to gemicitabine in pancreatic cancer cells,and down regulating hENT1 can decrease the chemotherapy sensitivity.Based on the mean hENT1 score(119.4),Two groups of hENT1 staining were separated using a cut-off of 120:low hENTl expression(staining score<＝120)and high hENT1 expression(staining score>120).Both DFS and OS of high hENT1 expression group are longer than low hENT1 expression group(21.75,95%CI 18.45-25.04 VS 12.48,95%CI 10.12-14.85)(15.44,95%CI 11.26-14.85 VS 8.24,95%CI 6.69-9.78)In the subsequent multivariate analysis,low hENT1 expression is an independence factor for poor prognosis.ConclusionhENTl expression is related with the chemotherapy sensitivity in pancreatic cancer cells.In gemcitabine-based chemotherapy,there is good relationship between hENTl expression and patients’ prognosis.hENTl expression may predict the patients’ response to gemcitabine-based chemotherapyBackgroundPatients suffering from pancreatic adenocarcinoma have a poor prognosis,with annually increasing morbidity.Besides chemotherapeutic resistance,lacking of prognostic marker also heavily hinder patients obtain long-term survival.It has been reported that CREPT related the the prognosis of some GI tumors.However,the relationship between CREPT expression and the cell proliferation,drug resistance,migration and invasion in pancreatic cancer cells are still noknown.This study was performed to detect the role of CREPT in pancreatic cancer cells.ObjectiveThis study was performed to detect the role of CREPT in pancreatic cancer cells.MethodsDetect CREPT expression level in 6 pancreatic caner cell lines.Construct CREPT high expression and/or low expression stable cell lines.Detect the role of CREPT in cell proliferation,drug resistance,migration and invasion.ResultsIn the six pancreatic caner cell lines,the higher CREPT expression was detected in T3M4 cell line and the lower CREPT expression was detected in MIA cell line.Through up and/or slince the CREPT gene,the CREPT overexpression stable cell line and the CREPT slince stable cell line were established.CREPT can increase pancreatic cancer cells gemcitabine chemoresistance.Down regulate CREPT can decrease cell proliferation,migration and invasion.While,Up regulate CREPT can not impove cell proliferation,migration and invasion.ConclusionSlince CREPT can inhibit cell proliferation,migration and invasion in pancreatic cancer cells.CREPT can increase pancreatic cancer cells gemcitabine chemoresistance.CREPT may be the prognostic marker for pancreatic cancer.