The prognosis and function study of F-box and WD-40 domain protein 7 in breast cancer
Objective To explore the clinical significance and function of F-box and WD-40 do-main 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 de-termined 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,x2=6.146,P＜0.05).In the BC patients with age ≥ 60 years old(90.333 vs.113.615,x=4.747,P＜0.05),right breast as the lesion site(107.150 vs.137.727,x2=4.685,P＜0.05),pathological T2(92.700 vs.114.760,x2=4.124,P＜0.05),lymph node metastasis(104.083 vs.132.211,P＜0.05),TNM stage Ⅲ(87.062 vs.130.333,x2=5.494,P＜0.05),estrogen receptor(ER)positive rate(97.381 vs.133.478,x2=4.902,P＜0.05)and human epidermal growth factor receptor-2(Her-2)positive rate(93.181 vs.131.727,x2=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 analy-sis(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=78.560,P＜0.05]and 39.523 times[(0.998±0.050)vs.(39.456±0.210),t=54.640,P＜0.05],respectively.Overexpression of FBXW7 significantly reduced the proliferation[The 4th day of MCF7 group:(1.639±0.045)vs.(1.141±0.842),t=10.400,P＜0.05;mDA-MB-231 group on the 2nd day:(0.519±0.030)vs.(0.410±0.025),t=5.447,P＜0.05;3rd day:(1.416±0.68)vs.(1.129±0.022),t=7.939,P＜0.05;4th day:(1.910±0.071)vs.(1.247±0.069),t=13.310,P＜0.05],colony for-mation[(211.333±7.039)vs.(92.667±3.681),t=21.120,P＜0.05;(133.000±7.348)vs.(28.333±3.858),t=17.830,P＜0.05],and migration of BC cell lines MCF7 and MDA-MB-231[(286.333±8.993)vs.(82.000±7.257),t=25.000,P＜0.05;(176.000±5.099)vs.(65.333±6.649),t=18.680,P＜0.05].Conclusion FBXW7 can be used as an indicators for BC patients and functions as a tumor suppressor gene in BC.
F-box and WD-40 domain protein 7Breast cancerPrognosisTumor suppres-sor
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