摘要
目的探讨乳腺癌蒽环类药物靶点TOP2A(DNA topoisomeraseⅡalpha)基因表达水平与HER2(human epidermal growth factor receptor 2)、PTEN(phosphatase and tensin homolog)基因表达及PI3K(phosphatidylinositol 3-kinase)基因突变的相关性,为乳腺癌预后及药物疗效判断提供参考依据。方法回顾性分析我院经病理确诊的96例乳腺癌患者的手术切除肿瘤样本,通过分支DNA-液相芯片法检测TOP2A、HER2、PTEN基因的mRNA表达水平,通过xTAG液相芯片法检测PI3K基因突变,并对检测结果应用SPSS19.0软件进行Spearman相关分析,明确TOP2A与HER2通路基因的关系。结果蒽环类药物靶点TOP2A和HER2存在共表达性,HER2基因高表达时,TOP2A趋向于高表达(P=0.01)。PTEN表达与TOP2A表达无统计学差异性关系。PI3K突变与TOP2A表达存在正相关关系,PI3K突变时TOP2A趋向于高表达(P=0.004)。结论蒽环类药效预测因子TOP2A与HER2通路的关键因子相关,提示HER2表达和PI3K突变是调控TOP2A表达的重要因素,为研究化疗药物耐药提供了重要的参考依据。
Objective To study the correlation of expression of DNA topoisomerase Ⅱ alpha （TOP2A）with expressions of human epidermal growth factor receptor 2 （HER2）and phosphatase and tensin homolog （PTEN）and gene mutation of phosphatidylinositol 3-kinase （PI3K）in breast cancer so as to provide reference for prognosis of the cancer and evaluation of drug efficiency.Methods This study enrolled totally 96 breast cancer patients. Tumor specimens were resected.The gene expressions of TOP2A,HER2 and PTEN were analyzed using branched DNA-liquid-chip,and PI3K gene mutation was detected by xTAG-liquid-chip.Correlations between gene expressions and gene mutation were further explored by Spearman correlation analysis so as to clarify the relationship between TOP2A and HER2 signaling pathway gene.Results Co-expression of TOP2A and HER2 was strong,and TOP2A tended to be highly expressed in the presence of high expression of HER2 （P =0.01）.The expression of PTEN was not significantly correlated with the expression of TOP2A,whereas the mutation of PI3K had a positive association with the high expression of TOP2A （P =0.004）.Conclusion Anthracycline drug resistance factor TOP2A may be related to the critical factors of HER2 signaling pathway,suggesting that HER2 expression and PI3K mutation may be key factors in regulation of TOP2A expression,which would provide important evidence for chemotherapeutic resistance.
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2015年第4期519-522,557,共5页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.81173613)~~
关键词
乳腺癌
TOP2A
HER2
蒽环类药物
breast cancer
DNA topoisomerase Ⅱ alpha （TOP2A）
human epidermal growth factor receptor 2（HER2）
anthracycline
