摘要
目的探讨果糖双磷酸酶-1(FBP1)在乳腺癌化疗耐药中的作用及其临床意义.方法构建乳腺癌表柔比星耐药细胞株,实时定量聚合酶链反应(Real-time PCR)和蛋白质印迹法(Western blot)检测其FBP1基因及蛋白改变,在耐药细胞株中过表达FBP1基因,检测其化疗敏感性的改变.收集2011年1月至2012年12月在浙江肿瘤医院乳腺外科接受治疗的62例新辅助化疗病例,免疫组织化学检测其乳腺癌组织内FBP1表达,统计其与新辅助化疗疗效的相关性,生存分析FBP1表达高低对乳腺癌预后的影响.计量资料采取均值±标准差(Mean±SD)表示,两样本均数比较采用t检验,FBP1在乳腺癌组织中表达水平与化疗疗效的相关性采用Spearman等级相关性检验,Log-rank检验分析生存差异.结果耐药MCF-7细胞较亲本MCF-7细胞内FBP1 mRNA(t=13.100,P<0.01)和蛋白表达均显著下调(t=16.250,P<0.05),过表达FBP1基因可以改善耐药细胞株的化疗敏感性.在乳腺癌组织内,FBP1高表达组,化疗疗效效为完全缓解(CR)、部分缓解(PR)、稳定(SD)和疾病进展(PD)的病例分别为6(20.0%)、6(53.3%)、6(20.0%)、6(6.7%) FBP1低表达组,CR、PR、SD和PD的病例分别为3(9.3%)、9(28.1%)、12(37.5%)、8(25.0%),Spearman等级相关分析显示FBP1表达与疗效呈正相关(R=0.301,P<0.05),FBP1低表达组提示乳腺癌5年无复发生存期(P<0.05)和5年总生存期(P<0.05)均较FBP1高表达组明显降低.结论 FBP1低表达提示乳腺癌表柔比星化疗耐药,与不良临床预后明显相关.
Objective To explore the role of fructose-1, 6-bisphosphatase 1 (FBP1) in the chemo-resistance of breast cancer and its significance in prognosis. MethodsDetecting the different expression of FBP1 mRNA and protein in wild-type MCF-7 and epirubicin resistant MCF-7 by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting. Detecting the chemo-sensitivity of change in epirubicin resistant MCF-7 cells after restoration the FBP1 expression. Detecting the FBP1 expression in breast cancer by immunohistochemistry and analyzing its correlation with chemotherapy response. Statistically analyzing the significance of FBP1 expression in disease free survival and overall survival of breast cancer patients. ResultsBoth FBP1 mRNA (t=13.100, P<0.01) and protein (t=16.250, P<0.05) were significantly decreased in epirubicin resistant MCF-7 cells than in parental MCF-7 cells, restoration of FBP1 expression in resistant MCF-7 cells improves its chemo-sensitivity. Breast cancer patients with high FBP1 expression achieves higher frequency of complete response (CR) 6 (20.0%), and partial response (PR) 6 (53.3%) than those with low FBP1 expression, FBP1 expression is positively correlated with chemotherapy response (R=0.355, P<0.01) in addition, 5-year disease free survival (79.3%) and overall survival (92.3%) in breast cancer patients with high FBP1 expression is significantly higher than those with low FBP1 expression, 58.1% and 77.3% respectively. ConclusionLow expression of FBP1 is a biomarker of chemo-resistance and is correlated with decreased disease free survival and overall survival of breast cancer.
作者
夏想厚
尹文娟
扈杰杰
竺美珍
秦承东
俞洋
Xia Xianghou;Yin Wenjuan;Hu Jiejie;Zhu Meizhen;Qin Chengdong;Yu Yang(Department of Breast Surgery,Zhejiang Cancer Hospital,Hangzhou 310022,China;Department of Pathology,Zhejiang Cancer Hospital,Hangzhou 310022,China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2019年第7期1287-1289,共3页
Chinese Journal of Experimental Surgery
基金
浙江省医药卫生科教计划项目(2017ZD011、2018KY280、2018KY283、2019KY329、2019KY335)
浙江省自然科学基金(LY19H160005).
关键词
果糖二磷酸酶-1
乳腺癌
化疗
化疗耐药
Fructose-1, 6-bisphosphatase 1
Breast cancer
Chemotherapy
Chemo-resistance
