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

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

Dongfeng Sun  1 , Chengyu Chen  1 , Wensi Hu  1 , Chenxi Zhong  2 , Limin Fan  2 , Xiaoming Song  1 , Zhibo Gai  3
Affiliations

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

Dongfeng Sun et al. Onco Targets Ther. .

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.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Immunohistochemical staining of normal and esophageal cancer specimens in which antibodies to AIP1 (A–C), CD34 (D–F), and VEGFR2 (G–I) were used. Notes: Representative immunostaining images of (A, D, G) normal adjacent tissues and (B, C, E, F, H, I) ESCC tumor tissues. (B and C) Distribution of AIP1 in ESCC tumor tissues revealed diffuse staining of membranes and cytoplasm of ESCC tumor tissues. (C) Low density of AIP1 located in ESCC tissues. (D–F) Immunohistochemical staining of CD34, which was used to mark endothelial cells and to evaluate MVD in different tissues. (E) Low MVD in ESCC tissues. (F) High MVD in ESCC tissues. (H and I) Different distribution of VEGFR2 in ESCC tumor tissues. Scale bar=100 µm. Abbreviations: AIP1, ASK1-interacting protein-1; ESCC, esophageal squamous cell carcinoma; MVD, microvessel density; VEGFR2, vascular endothelial growth factor receptor 2.
Figure 2
Figure 2
Cross-correlation analyses revealed strong relationships among the expressions of AIP1 and VEGFR2 and MVD in ESCC. Notes: (A) Significant correlation was observed between the low density of AIP1 and high MVD in ESCC tumor tissues (P<0.0001). (B) Significant correlation was observed between the high VEGFR2 in ESCC tumor tissues and low density of AIP1 (P<0.01). (C) Significant correlation was observed between the density of the expression of VEGFR2 and MVD in ESCC tumor tissues (P=0.0349). Abbreviations: AIP1, ASK1-interacting protein-1; ESCC, esophageal squamous cell carcinoma; MVD, microvessel density; VEGFR2, vascular endothelial growth factor receptor 2.
Figure 3
Figure 3
Kaplan–Meier survival curves of patients stratified according to AIP1 expression (A and B). Patients with low density of AIP1 in tumor tissues had a poor overall survival (P<0.05). Abbreviation: AIP1, ASK1-interacting protein-1.
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References

    1. Wang M, Smith JS, Wei WQ. Tissue protein biomarker candidates to predict progression of esophageal squamous cell carcinoma and precancerous lesions. Ann N Y Acad Sci. 2018 - PubMed
    1. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11(17):6190–6197. - PubMed
    1. Mariette C, Balon JM, Piessen G, Fabre S, van Seuningen I, Triboulet JP. Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer. 2003;97(7):1616–1623. - PubMed
    1. Law S, Kwong DL, Kwok KF, et al. Improvement in treatment results and long-term survival of patients with esophageal cancer: impact of chemoradiation and change in treatment strategy. Ann Surg. 2003;238(3):339–347. - PMC - PubMed
    1. Okawa T, Naomoto Y, Nobuhisa T, et al. Heparanase is involved in angiogenesis in esophageal cancer through induction of cyclooxygenase-2. Clin Cancer Res. 2005;11(22):7995–8005. - PubMed