Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer

Handa,Tadashi; Katayama,Ayaka; Yokobori,Takehiko; Yamane,Arito; Fujii,Takaaki; Obayashi,Sayaka; Kurozumi,Sasagu; Kawabata-Iwakawa,Reika; Gombodorj,Navchaa; Nishiyama,Masahiko; Asao,Takayuki; Shirabe,Ken; Kuwano,Hiroyuki; Oyama,Tetsunari

doi:10.3892/ijo.2019.4675

Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer

Authors:
- Tadashi Handa
- Ayaka Katayama
- Takehiko Yokobori
- Arito Yamane
- Takaaki Fujii
- Sayaka Obayashi
- Sasagu Kurozumi
- Reika Kawabata-Iwakawa
- Navchaa Gombodorj
- Masahiko Nishiyama
- Takayuki Asao
- Ken Shirabe
- Hiroyuki Kuwano
- Tetsunari Oyama
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Affiliations: Department of Diagnostic Pathology, Gunma University, Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan, Department of Innovative Cancer Immunotherapy, Gunma University, Maebashi, Gunma 371-8511, Japan, Yamane Clinic of Internal Medicine, Sugito, Saitama 345-0046, Japan, Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma 371-8511, Japan, Department of Molecular Pharmacology and Oncology, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371-8511, Japan, Big Data Center for Integrative Analysis, Gunma University Initiative for Advance Research (GIAR), Maebashi, Gunma 371-8511, Japan
Published online on: January 4, 2019 https://doi.org/10.3892/ijo.2019.4675
Pages: 833-844
Copyright: © Handa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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