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

Onco Targets Ther. 2018 Nov 1:11:7699-7707. doi: 10.2147/OTT.S178131. eCollection 2018.

Abstract

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: ASK1-interacting protein-1; angiogenesis; esophageal squamous cell carcinoma; microvessel density.