CD24在三阴性乳腺癌中的表达及与EMT的关系

Expression of CD24 in triple negative breast cancer and its relationship with EMT

目的:探讨三阴性乳腺癌(triple negative breast cancer,TNBC)中CD24表达与临床病理特征的关系,分析其表达对上皮间质转化(EMT)的影响。方法:通过基因表达谱动态分析数据库(Gene expression Profiling Interactive Analysis,GEPIA)分析CD24在不同乳腺癌亚型中的表达情况;Kaplan-Meier Plotter在线数据库分析CD24的表达与乳腺癌患者相关预后因素的关系;收集73例三阴性乳腺癌患者癌组织病理切片,免疫组化法检测分析CD24的表达与三阴性乳腺癌临床病理特征的关系;流式细胞术分选CD24^(high/low)细胞亚群,Transwell小室检测CD24^(high/low)细胞不同的迁移能力,Western blot检测CD24^(high/low)与上皮间质转化相关蛋白的变化关系。结果:与正常乳腺组织相比,CD24在癌组织中明显高表达,其在TNBC组织中的表达量最高(P<0.05)。与CD24^(low)组比较,CD24^(high)组患者的预后更差(P<0.05)。免疫组化提示,CD24在TNBC中高表达,阳性率达82.19%,CD24的表达与患者的年龄、肿瘤大小、组织学分级、TNM分期均无关(P>0.05),仅与淋巴结有无转移相关(P<0.05)。Transwell小室结果表明,CD24^(low)细胞群的迁移能力明显弱于CD24^(high)细胞群(t=22.814,P<0.05)。Western blot结果显示,CD24^(low)组的E-cadherin和β-catennin蛋白水平明显低于CD24^(high)组,而N-cadherin和Vimentin蛋白水平明显高于CD24^(high)组,以上指标差异具有统计学意义(均P<0.05)。结论:CD24在三阴性乳腺癌中高表达,其表达与EMT相关蛋白相关,可能参与肿瘤的远处转移,可作为评估患者预后的潜在指标。

Objective:To investigate the relationship between CD24 expression and clinicopathological features in triple negative breast cancer(TNBC),and to analyze the effect of CD24 expression on epithelial mesenchymal transformation(EMT).Methods:The expression of CD24 in different breast cancer subtypes was analyzed by Gene expression Profiling Interactive Analysis database(GEPIA).Kaplan-Meier Plotter database was used to analyze the relationship between CD24 expression and related prognostic factors in breast cancer patients.Immunohistochemistry was used to detect the expression of CD24 protein in paraffin embedded tissues from 73 cases of TNBC.The relationship between CD24 expression and clinicopathological parameters was analyzed.Flow cytometry was used to separate CD24^(high/low) cells.Transwell chamber was used to detect different migration capacities of CD24^(high/low),and Western blot was used to detect the relationship between CD24^(high/low) and changes of EMT-related proteins.Results:Compared with normal breast tissue,the expression of CD24 was significantly higher in cancer tissue,and the expression level of CD24 was the highest in TNBC tissue(P<0.05).Compared with CD24^(low) group,the prognosis of patients with CD24^(high) group was worse(P<0.05).Immunohistochemistry showed that CD24 was highly expressed in TNBC,with a positive rate of 82.19%.The expression of CD24 was not related to age,tumor size,histological grade and TNM stage(P>0.05),but was only related to lymph node metastasis(P<0.05).Transwell chamber results showed that the migration ability of CD24^(low) cells was significantly weaker than that of CD24^(high) cells(t=22.814,P<0.05).Western blot results showed that the protein levels of E-cadherin andβ-catennin in the CD24^(low) group were significantly lower than those in the CD24^(high) group,while the protein levels of N-cadherin and Vimentin were significantly higher than those in the CD24^(high)group.The differences of the above indexes were statistically significant(all P<0.05).Conclusion:CD24 is highly expressed in TNBC,EMT phenotype is associated with TNBC cells and is involved in distant metastasis,which may be a potential indicator in assessing patient prognosis.