羧肽酶A4调控三阴性乳腺癌干性及上皮-间质转换的机制  

Mechanism of carboxypeptidase A4 regulation of stem and epithelial-mesenchy mal transition in triple negative breast cancer

作　　者：李映东 王铁延[2] 欧琴[1] 章书铭 李文仿[1] LIYindong;WANG Tieyan;OU Qin;ZHANG Shuming;LI Wenfang(Breast and Thyroid Center,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan 442000,Hubei,China;Department of Pathology,Taihe Hospital Affiliated to Hubei University of Medicine,Shiyan 442000,Hubei,China)

机构地区：[1]湖北医药学院附属太和医院乳腺甲状腺中心,湖北十堰442000 [2]湖北医药学院附属太和医院病理科,湖北十堰442000

出　　处：《西部医学》2023年第9期1270-1275,1281,共7页Medical Journal of West China

基　　金：湖北省教育厅指导项目(B2019111)。

摘　　要：目的探讨三阴性乳腺癌(TNBC)中羧肽酶A4(CPA4)的表达及临床病理意义。方法收集我院2019年1月—2021年10月手术切除经临床病理诊断确诊的TNBC早期患者168例,同期非TNBC共40例,同期乳腺包块切除后诊断乳腺增生组织20例。用免疫组化方法检测TNBC组织中CPA4,干性相关蛋白醛脱氢酶1、NANOG,上皮-间质转换(EMT)相关蛋白E-cadherin、Vimentin表达。分析168例TNBC中CPA4表达与临床病理指标关系。敲除MDA-MB-231细胞中CPA4(siCPA4),观察对细胞克隆形成、细胞成球、侵袭及迁移影响,Western Blot检测相关蛋白表达。结果TNBC组织中CPA4表达率57.14%,明显高于非TNBC的37.5%,差异有统计学意义(χ^(2)=5.009,P=0.025),TNBC中CPA4表达明显高于乳腺增生组织的20%,差异具有统计学意义(χ^(2)=9.850,P=0.002)。TNBC中CPA4表达与患者年龄、绝经状态、脉管浸润、肿瘤大小、组织学分级、TNM分期差异无统计学意义。CPA4阳性组淋巴结转移率为59.4%,CPA4阴性组淋巴结转移率为38.9%,差异具有统计学意义(χ^(2)=6.908,P=0.009)。CPA4阳性组Ki-67为84.4%,而CPA4阴性组Ki-67为70.8%,差异具有统计学意义(χ^(2)=4.481,P=0.034)。168例TNBC中CPA4表达与患者ALDH1(χ^(2)=1.575,P=0.209)无关,但与NANOG(χ^(2)=4.205,P=0.040)、E-cadherin(χ^(2)=11.764,P=0.001)、Vimentin(χ^(2)=4.797,P=0.029)、EGFR(χ^(2)=4.057,P=0.044)差异有统计学意义。siCPA4抑制TNBC克隆形成,细胞成球,迁移与侵袭,抑制ALDH-1、NANOG、vimentin表达,促进E-cadherin表达。结论CPA4在TNBC干性进展及EMT转换过程中可能发挥一定作用,CPA4可能是反应TNBC侵袭、转移表型的重要治疗靶点。Objective To investigate the expression and clinicopathological significance of carboxypeptidase A4(CPA4)in triple negative breast cancer(TNBC).Methods The expression of CPA4,aldehyde dehydrogenase 1,NANOG,E-cadherin and Vimentin in TNBC tissues were detected by immunohistochemistry.The relationship between CPA4 expression and clinicopathological indicators in 168 cases of TNBC was analyzed.CPA4 was knocked out in MDA-MB-231 cells to observe the effects on cell proliferation,invasion and migration.The expression of related proteins was detected by Western Blot.Results The expression rate of CPA4 in TNBC tissues was 57.14%,significantly higher than that in non-TNBC tissues(37.5%),the difference was statistically significant(χ^(2)=5.009,P=0.025).CPA4 expression in TNBC was significantly higher than that in breast hyperplasia tissues by 20%,and the difference was statistically significant(χ^(2)=9.850,P=0.002).The expression of CPA4 in 168 TNBC patients was not associated with ALDH1(χ^(2)=1.575,P=0.209),but with NANOG(χ^(2)=4.205,P=0.040),E-cadherin(χ^(2)=11.764,P=0.001),Vimentin(χ^(2)=4.797,P=0.029),EGFR(χ^(2)=4.057,P=0.044).SiCPA4 inhibits TNBC clone formation,migration and invasion,inhibits the expression of ALDH-1,NANOG,vimentin and promotes the expression of E-cadherin.Conclusion CPA4 might play a role in the stem progression of TNBC and the transformation of EMT,and CPA4 might be an important therapeutic target for TNBC invasion and metastasis phenotypes.

关 键 词：羧肽酶A4 三阴性乳腺癌 干性 上皮-间质转换 

分 类 号：R737.9[医药卫生—肿瘤]