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Low expression level of ASK1-interacting protein-1 correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer

Authors Sun D, Chen C, Hu W, Zhong C, Fan L, Song X, Gai Z

Received 24 June 2018

Accepted for publication 12 September 2018

Published 1 November 2018 Volume 2018:11 Pages 7699—7707

DOI https://doi.org/10.2147/OTT.S178131

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava


Dongfeng Sun,1 Chengyu Chen,1 Wensi Hu,1 Chenxi Zhong,2 Limin Fan,2 Xiaoming Song,1 Zhibo Gai3

1Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, People’s Republic of China; 2Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai 200030, People’s Republic of China; 3Joint Pharmacology Center, University Hospital Zurich and Liaocheng People’s Hospital, Liaocheng 252000, People’s Republic of China

Objective: To investigate the expression of tumor suppressor protein ASK1-interacting protein-1 (AIP1) in human esophageal squamous cell carcinoma (ESCC) and its role in tumor progression, angiogenesis, and prognosis.
Methods: A total of 117 biopsy samples were obtained from ESCC patients. None of the patients had distant metastasis before surgery, and did not receive preoperative chemotherapy or radiotherapy. Immunohistochemistry was used to detect the expression of AIP1 protein and vascular endothelial growth factor receptor 2 (VEGFR2) in ESCC specimens collected from 117 patients who underwent esophageal cancer radical surgery. Microvessel density (MVD) was evaluated by immunohistochemical staining of vascular endothelial CD34. The correlation between AIP1 protein and clinicopathological characteristics, tumor angiogenesis, and prognosis was analyzed.
Results: The downregulation of AIP1 protein in esophageal carcinoma tissues was detected in 63 cases. This downregulation significantly correlated with lymph node metastasis, clinicopathological staging, and tumor MVD (P<0.05). Survival analysis showed that ESCC patients with a low expression of AIP1, a high expression of VEGFR2, and a high level of MVD had a lower 5-year survival rate (P<0.05). Multivariate analysis confirmed that the downregulation of AIP1 significantly affected patient survival.
Conclusion: The downregulation of AIP1 correlated with ESCC progression, tumor angiogenesis, and poor prognosis. AIP1 could be a promising biomarker for predicting ESCC prognosis and a potential target for anti-angiogenic therapy.

Keywords:
esophageal squamous cell carcinoma, angiogenesis, ASK1-interacting protein-1, microvessel density

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