Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer
Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer
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DOI：
10.3892/ijo.2019.4675
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发表时间：
2019-03-01
影响因子：
5.2
通讯作者：
Oyama, Tetsunari
中科院分区：
文献类型：
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作者：
Handa, Tadashi;Katayama, Ayaka;Oyama, Tetsunari
本研究利用全转录组分析和慢病毒短发夹RNA筛选文库，将羧肽酶A4（carboxypeptidase A4，CPA 4）作为乳腺癌的新标志物和三阴性乳腺癌（triple-negative breast cancer，TNBC）的治疗靶点。应用免疫组化方法检测221例乳腺癌组织中CPA 4、雌激素受体、孕激素受体、人表皮生长因子受体2、Ki 67、表皮生长因子受体、细胞角蛋白5/6、乙醛脱氢酶1、分化簇（CD）44、CD 24、claudins、E-cadherin、vimentin和雄激素受体的表达。利用RNA干扰方法分析了CPA 4对TNBC细胞活力和迁移能力的影响。检测到CPA 4表达增加，特别是在癌组织细胞的细胞质中。此外，TNBC病例中的高CPA 4表达与E-钙粘蛋白的低表达和癌症干细胞标志物（高CD 44/低CD 24）的表达相关。与CPA 4低表达的患者相比，CPA 4高表达的TNBC患者的预后明显较差。值得注意的是，存活率和迁移降低，但在CPA 4抑制的TNBC细胞中E-钙粘蛋白表达上调。目前的数据表明，CPA 4可能是一种新的诱导上皮-间充质转化，其特征在于下调E-cadherin和间充质表型。总之，CPA 4可能是具有侵袭性表型的TNBC中预后不良的标志物和有希望的治疗靶点。
Using whole transcriptome analysis and a lentiviral short hairpin RNA screening library, carboxypeptidase A4 (CPA4) was identified as a novel marker in breast cancer and a therapeutic target in triple-negative breast cancer (TNBC) in the present study. Immunohistochemistry was used to evaluate the presence of CPA4, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki67, epidermal growth factor receptor, cytokeratin 5/6, aldehyde dehydrogenase 1, cluster of differentiation (CD)44, CD24, claudins, E-cadherin, vimentin and androgen receptor in 221 cases of breast cancer, including 68 TNBC cases. The effects of CPA4 on the viability and migration ability of TNBC cells were analyzed using RNA interference methods. Increased CPA4 expression, specifically in the cytoplasm of cancer tissue cells, was detected. Furthermore, high CPA4 expression in TNBC cases was associated with low expression of E-cadherin and with the expression of cancer stem cell markers (high CD44/low CD24). Patients with TNBC and high levels of CPA4 expression had a significantly poorer prognosis compared with those with low CPA4 expression. Notably, viability and migration were reduced, but E-cadherin expression was upregulated in CPA4-suppressed TNBC cells. The present data suggested that CPA4 may be a novel inducer for epithelial-mesenchymal transition, which is characterized by the downregulation of E-cadherin and mesenchymal phenotypes. To conclude, CPA4 may be a marker for poor prognosis and a promising therapeutic target in TNBC with aggressive phenotypes.