羧肽酶A4调控三阴性乳腺癌干性及上皮-间质转换的机制
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湖北省教育厅指导项目(B2019111)


Mechanism of carboxypeptidase A4 regulation of stem and epithelial-mesenchy mal transition in triple negative breast cancer
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    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(χ2=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(χ2=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(χ2=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(χ2=4.481,P=0.034)。168例TNBC中CPA4表达与患者ALDH1(χ2=1.575,P=0.209)无关,但与NANOG(χ2=4.205,P=0.040)、E-cadherin(χ2=11.764,P=0.001)、Vimentin(χ2=4.797,P=0.029)、EGFR(χ2=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。

    Abstract:

    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 (χ2=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 (χ2=9.850, P=0.002). The expression of CPA4 in 168 TNBC patients was not associated with ALDH1 (χ2=1.575, P=0.209), but with NANOG (χ2=4.205, P=0.040), E-cadherin (χ2=11.764, P=0.001), Vimentin (χ2=4.797, P=0.029), EGFR (χ2=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.

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  • 在线发布日期: 2023-09-18
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