AP1S1在乳腺癌中的表达及其对化疗耐药的影响  

Role of AP1S1 in inducing chemotherapy resistance in breast cancer

作　　者：李晨欣 李启基 张娣 杨颖倩 张煜浩 王锐 叶丽平 LI Chenxin;LI Qiji;ZHANG Di;YANG Yingqian;ZHANG Yuhao;WANG Rui;YE Liping(Scientific Research Center,the Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,Guangdong 518107,China;Department of Orthopaedic Surgery,the Seventh Afiliated Hospital,Sun Yat-sen University,Shenzhen,Guangdong 518107,China;School of Medicine,Sun Yat-sen University,Shenzhen,Guangdong 518107,China)

机构地区：[1]中山大学附属第七医院科研中心,广东深圳518107 [2]中山大学附属第七医院骨科,广东深圳518107 [3]中山大学医学院,广东深圳518107

出　　处：《热带医学杂志》2024年第6期776-782,800,I0002,共9页Journal of Tropical Medicine

基　　金：国家自然科学基金(82072905,82372907);广东省基础与应用基础研究基金(2022A1515011111,2023A1515030058)。

摘　　要：目的 探究接头相关蛋白复合物1亚基σ1(AP1S1)基因表达水平与乳腺癌化疗患者预后之间的相关性,分析AP1S1在乳腺癌化疗耐药中的作用。方法 采用生物信息学方法,对癌症基因组图谱(TCGA)数据库中的乳腺癌患者和乳腺正常组织的AP1S1表达水平差异进行分析。运用Kaplan-Meier生存分析法,探究AP1S1表达水平与乳腺癌化疗患者无复发生存预后的关联。通过细胞培养、RNA提取、实时荧光定量PCR、蛋白质免疫印迹(Western blot)分析及药物敏感性实验等多种实验手段,基于AP1S1高表达的乳腺癌细胞模型,研究AP1S1基因高表达对乳腺癌细胞化疗耐药的影响,并考察AP1S1过表达对肿瘤细胞干性及上皮-间充质转化(EMT)特性标志物表达的作用。结果 乳腺癌组织中AP1S1基因的表达水平显著高于正常组织,差异有统计学意义(P<0.05)。在肿瘤不同分期,AP1S1基因的表达水平均表现出显著高于正常组织,差异均有统计学意义(P均<0.05);其中4期肿瘤的过表达水平更高,差异有统计学意义(P<0.05)。管腔(Luminal)型、人类表皮生长因子2(HER2)阳性型和三阴型乳腺癌组织较正常组织均表现出AP1S1基因高表达,差异均有统计学意义(P均<0.05);其中在HER2阳性型和三阴型乳腺癌组织中AP1S1表达水平更高,差异均有统计学意义(P均<0.05)。Kaplan-Meier生存分析发现,AP1S1高表达的乳腺癌患者在化疗后无复发生存期显著短于低表达组,差异有统计学意义(P=0.038);在三阴型、HER2阳性乳腺癌患者中,AP1S1高表达与化疗后预后不良显著相关(P=0.037、0.017);Luminal B型患者中,AP1S1高表达与较长的无复发生存期显著相关(P=0.007)。实时荧光定量PCR显示,与对照组比较,在AP1S1过表达的细胞系CAL-51-oe-AP1S1、Hs-578T-oe-AP1S1中AP1S1转录水平显著上调,差异均有统计学意义(t=23.51、6.22,P均<0.05);Western blot结果显示,与对照组比较,在AP1S1过表达的细胞系CAL-51-oe-AP1SObjective To explore the correlation between the expression level of adaptor related protein complex 1 subunit sigma 1(AP1S1) gene and the prognosis of breast cancer patients undergoing chemotherapy, and analyze the role of AP1S1in chemotherapy resistance of breast cancer. Methods The expression of AP1S1 between breast cancer patients and breast normal tissues in The Cancer Genome Atlas(TCGA) database was analyzed by bioinformatics. Kaplan-Meier survival analysis was used to explore the association between AP1S1 expression level and relapse-free survival prognosis of breast cancer patients undergoing chemotherapy. Through cell culture, RNA extraction, real-time fluorescent quantitative PCR, Western blot analysis and drug sensitivity test, and other experimental methods, based on the breast cancer cell model with high expression of AP1S1, the effect of high expression of AP1S1 gene on chemotherapy resistance of breast cancer cells was revealed. The effect of overexpression of AP1S1 on the expression of stem and epithelial-mesenchymal transformation(EMT) markers in tumor cells was investigated. Results significantly higher than that in normal tissue;the difference was statistically significant(P<0.05). At different tumor stages, the expression level of AP1S1 gene was significantly higher than that of normal tissue, with statistical significance(all P<0.05). Among them, the overexpression level of AP1S1 gene of stage 4 tumors was higher, and the difference was statistically significant(P<0.05). Luminal,human epidermal growth factor receptor 2(HER2)-positive and triple-negative breast cancer tissues showed high expression level of AP1S1 gene compared with normal tissues, with statistical significance(all P<0.05). The expression levels of AP1S1 were higher in HER2-positive and triple-negative breast cancer tissues, and the differences were statistically significant(both P<0.05). Kaplan-Meier survival analysis showed that the relapse-free survival of breast cancer patients with high AP1S1 expression after chemotherapy

关 键 词：AP1S1 乳腺癌 多西紫杉醇 化疗耐药 

分 类 号：R737.9[医药卫生—肿瘤]