F框/WD-40域蛋白7在乳腺癌预后预测中的价值及功能研究  

The prognosis and function study of F-box and WD-40 domain protein 7 in breast cancer

作　　者：罗飞[1] 罗宁[2] 李晓宇[3] 贾红燕[4] Luo Fei;Luo Ning;Li Xiaoyu;Jia Hongyan(Department of Breast Surgery,Affiliated Cancer Hospital of Shanxi Medical University,Shanxi Provincial Cancer Hospital,Taiyuan 030013,China;Department of Radiation Oncology,Shanxi Provincial Cancer Hospital,Taiyuan 030013,China;Department of Tumor Biobank,Shanxi Provincial Cancer Hospital,Taiyuan 030013,China;Department of Breast Surgery,the First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学附属肿瘤医院,山西省肿瘤医院乳腺外科,太原030013 [2]山西省肿瘤医院放疗科,太原030013 [3]山西省肿瘤医院肿瘤生物样本库,太原030013 [4]山西医科大学第一医院乳腺外科,太原030001

出　　处：《中华实验外科杂志》2024年第6期1265-1269,共5页Chinese Journal of Experimental Surgery

基　　金：山西省自然科学基金(202303021221237);山西省肿瘤医院硕导伴飞基金(SD2023014)。

摘　　要：目的探究F框/WD-40域蛋白7(FBXW7)在乳腺癌(BC)发生发展中的临床意义及功能。方法利用免疫组织化学技术对BC组织芯片中FBXW7的表达进行检测,受试者工作特征曲线(ROC)曲线确定FBXW7表达的阈值,使用Kaplan-Meier生存分析和比例风险回归模型(COX)预测FBXW7表达与患者预后的关系。向BC细胞系MCF7和MDA-MB-231转染pcDNA3-FBXW7wt质粒,实时荧光定量聚合酶链反应(qPCR)验证过表达效率。通过噻唑蓝(MTT)法和集落形成实验检测细胞增殖;可穿透性细胞培养小室检测细胞迁移。统计学方法分别采用独立样本t检验和方差分析。结果FBXW7在BC组织中的表达低于癌旁正常组织(8.537±0.536比9.619±0.360,t=21.080,P<0.05),低表达与BC患者预后差相关(104.143比133.714,χ^(2)=6.146,P<0.05),且在年龄≥60岁(90.333比113.615,χ^(2)=4.747,P<0.05)、右乳为病灶部位(107.150比137.727,χ^(2)=4.685,P<0.05)、病理T2(92.700比114.760,χ^(2)=4.063,P<0.05)、有淋巴结转移(104.083比132.211,χ^(2)=4.124,P<0.05)、TNMⅢ期(87.062比130.333,χ^(2)=5.494,P<0.05)、雌激素受体(ER)阳性(97.381比133.478,χ^(2)=4.902,P<0.05)和人表皮生长因子受体2(Her-2)阳性(93.181比131.727,χ^(2)=6.219,P<0.05)的BC人群中,FBXW7低表达患者的总生存期明显短于FBXW7高表达患者。单因素[比值比(OR):3.374;95%可信区间(CI):1.213~9.382,P<0.05]和多因素COX分析(OR:3.335;95%CI:1.062~10.476;P<0.05),结果显示FBXW7是BC患者生存状态的危险因素。MCF7和MDA-MB-231细胞FBXW7过表达效率分别为67.129倍[(0.998±0.055)比(66.972±0.423),t=78.560,P<0.05]和39.523倍[(0.998±0.050)比(39.456±0.210),t=54.640,P<0.05]。过表达FBXW7可显著抑制BC细胞系MCF7和MDA-MB-231细胞的增殖[MCF7组第4天为(1.639±0.045)比(1.141±0.842),t=10.400,P<0.05;MDA-MB-231组第2天为(0.519±0.030)比(0.410±0.025),t=5.447,P<0.05;第3天为(1.416±0.68)比(1.129±0.022),t=7.939,P<0.05;第4天为(1.910±0.071)比(1.247±0.069),t=13.310,P<0.05]、克隆形成[(211Objective To explore the clinical significance and function of F-box and WD-40 domain protein 7(FBXW7)in the onset and progression of breast cancer(BC).Methods The expression of FBXW7 in BC tissue microarray was detected using immunohistochemistry.To determine the relationship between FBXW7 expression and patient prognosis,we employed Kaplan-Meier survival analysis and the proportional hazards model(COX)proportional hazard regression model.The pcDNA3-FBXW7wt plasmid was transfected into the BC cell lines MCF7 and MDA-MB-231,and the overexpression efficiency was determined by qPCR.Cell proliferation was measured using the methyl thiazolyl tetrazolium(MTT)technique and the colony formation test.The Transwell method was used to detect cell migration.Two independent-sample t-test and ANOVA test were used for statistical analysis.Results FBXW7 expression in BC tissues was lower than in corresponding normal tissues(8.537±0.536 vs.9.619±0.360,t=21.080,P<0.05),which was related with a poor prognosis for BC patients(104.143 vs.133.714,χ^(2)=6.146,P<0.05).In the BC patients with age≥60 years old(90.333 vs.113.615,χ^(2)=4.747,P<0.05),right breast as the lesion site(107.150 vs.137.727,χ^(2)=4.685,P<0.05),pathological T2(92.700 vs.114.760,χ^(2)=4.124,P<0.05),lymph node metastasis(104.083 vs.132.211,P<0.05),TNM stageⅢ(87.062 vs.130.333,χ^(2)=5.494,P<0.05),estrogen receptor(ER)positive rate(97.381 vs.133.478,χ^(2)=4.902,P<0.05)and human epidermal growth factor receptor-2(Her-2)positive rate(93.181 vs.131.727,χ^(2)=6.219,P<0.05).The overall survival of patients with low expression of FBXW7 was significantly shorter than that of patients with high expression of FBXW7.By univariate[odds ratio(OR):3.374;95%confidence interval(CI):1.213-9.382,P<0.05]and multivariate COX analysis(OR:3.335;95%CI:1.062-10.476,P<0.05),the results showed that FBXW7 was a risk factor for the survival status of BC patients.The overexpression efficiency of FBXW7 in MCF7 and MDA-MB-231 cells was 67.129 times[(0.998±0.055)vs.(66.972±0.423),t=78

关 键 词：F框/WD-40域蛋白7 乳腺癌 预后 抑癌基因 

分 类 号：R737.9[医药卫生—肿瘤]