Effect of Y- box binding protein 1 overexpression on the prognosis of patients with intrahepatic cholangiocarcinoma undergoing postoperative adjuvant chemotherapy
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摘要: 目的探讨Y-box结合蛋白(YB)1过表达与肝内胆管癌患者术后辅助化疗预后的关系。方法收集2010年1月-2015年1月于安徽医科大学第一附属医院行手术治疗并辅助术后化疗的58例肝内胆管癌患者的石蜡标本。使用免疫组化方法检测肝内胆管癌组织中YB-1表达情况,使用噻唑蓝方法检测YB-1质粒转染肝内胆管癌细胞对吉西他滨药物敏感性的改变。q PCR检测YB-1质粒转染肝内胆管癌细胞后多药耐受基因表达改变情况。计量资料2组间比较采用独立样本t检验,多组间比较采用单因素方差分析;计数资料组间比较采用χ2检验;Kaplan-Meier方法计算生存曲线,生存分析采用log-rank检验。结果58例患者中44例(75.9%)患者YB-1在肝内胆管癌组织细胞胞浆中呈高表达(YB-1胞浆阳性组),14例(24.1%)YB-1胞浆阴性(YB-1胞浆阴性组);44例YB-1胞浆阳性患者中有18例(40.9%)癌组织的细胞中出现YB-1核染色阳性(YB-1胞核阳性组),其余40例为YB-1胞核阴性组。YB-1胞核阴性组患者术后辅助化疗生存时间显著长于YB-1胞核阳性组患者(63个月vs 2...Abstract: 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.
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Key words:
- biliary tract neoplasms /
- Y-box-binding protein 1 /
- drug tolerance /
- prognosis
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