Effect of Y- box binding protein 1 overexpression on the prognosis of patients with intrahepatic cholangiocarcinoma undergoing postoperative adjuvant chemotherapy

Objective To investigate the association between Y- box binding protein 1( YB- 1) overexpression and the prognosis of patients with intrahepatic cholangiocarcinoma( ICC) undergoing postoperative adjuvant chemotherapy.Methods The paraffin- embedded specimens were collected from 58 patients with ICC who underwent surgical treatment and postoperative adjuvant chemotherapy in The First Affiliated Hospital of Anhui Medical University from January 2010 to January 2015.Immunohistochemistry was used to measure the expression of YB- 1 in ICC tissue;after ICC cells were transfected with YB- 1 plasmid,the thiazolyl blue method was used to observe the change in gemcitabine sensitivity,and q PCR was used to observe the changes in the expression of multidrug resistance genes.The independent samples t- test was used for comparison of continuous data between two groups and a one- way analysis of variance was used for comparison of continuous data between multiple groups;the chi- square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to calculate survival rates and the log- rank test was used for survival difference analysis.Results Among the 58 patients,44( 75.9%) had high expression of YB- 1 in the cytoplasm of ICC cells( cytoplasm YB- 1 positive group) and 14( 24.1%)had no expression of YB- 1 in the cytoplasm of ICC cells( cytoplasm YB- 1 negative group).Of all patients in the cytoplasm YB- 1 positive group,18( 40.9%) also had positive nuclear expression of YB- 1( nuclear YB- 1 positive group);the other 40 patients had no nuclear expression of YB- 1( nuclear YB- 1 negative group).The nuclear YB- 1 negative group had a significantly longer survival time than the nuclear YB- 1 positive group( 63 months vs 28 months,χ~2= 17.99,P < 0.05).In the control plasmid group,the half- maximal inhibitory concentration( IC_(50)) of gemcitabine in HCCC- 9810 cells was 0.054 μmol,and in the p SG5- YB- 1 plasma transfection group,IC_(50) increased to 0.460 μmol after YB- 1 overexpression,which was 10 times higher than that in control plasmid group( P < 0.05).There was a significant increase in the YB- 1 transcriptional level after HCCC- 9810 cells were transfected with p SG5- YB- 1 plasmids( t =19.02,P < 0.05).After YB- 1 overexpression,HCCC- 9810 cells had significant increases in the transcriptional levels of multidrug resistance protein 1( MDR1) and multidrug resistance- associated protein 1( MRP1)( t = 13.34 and 11.35,both P < 0.05).Conclusion YB- 1 overexpression can be found in most ICC tissues,and nuclear positive expression of YB- 1 may indicate the poor effect of postoperative adjuvant chemotherapy,which may be associated with the increase in multidrug resistance after the expression of MDR1 and MRP1.