Expression levels of EPHB4, EFNB2 and caspase-8 are associated with clinicopathological features and progression of esophageal squamous cell cancer

Qianzhi Ni; Pingping Chen; Bing Zhu; Jingjing Li; Dong Xie; Xingyuan Ma

doi:10.3892/ol.2019.11160

Expression levels of EPHB4, EFNB2 and caspase-8 are associated with clinicopathological features and progression of esophageal squamous cell cancer

Oncol Lett. 2020 Jan;19(1):917-929. doi: 10.3892/ol.2019.11160. Epub 2019 Nov 28.

Authors

Qianzhi Ni^{1

2}, Pingping Chen³, Bing Zhu², Jingjing Li², Dong Xie^{2

4}, Xingyuan Ma¹

Affiliations

¹ School of Biotechnology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P.R. China.
² CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
³ Department of Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 45001, P.R. China.
⁴ NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100022, P.R. China.

Abstract

The upregulation of EPH receptor B4 (EPHB4) results in a survival advantage for tumor cells via the inhibition of the casapse-8-mediated apoptotic pathway, which begins from the cell membrane. The present study investigated the expression patterns of EPHB4, ephrin B2 (EFNB2) and caspase-8 in patients with esophageal squamous cell carcinoma (ESCC). The association between the expression patterns and certain clinicopathological characteristics of the patients was also determined. mRNA levels of EPHB4, EFNB2 and caspase-8 in paired primary ESCC samples and adjacent esophageal tissues collected from 96 patients with ESCC were quantified using quantitative PCR. Upregulation of EPHB4 and EFNB2 mRNA expression, and downregulation of caspase-8 mRNA were detected in ESCC samples compared with that in the adjacent esophageal tissues. The expression levels of EPHB4 and EFNB2 were positively correlated with each other, whereas the mRNA levels of both EPHB4 and EFNB2 exhibited a negative correlation with that of caspase-8. The mRNA levels of both EPHB4 and EFNB2 demonstrated a significant positive association with certain clinicopathological features of patients with ESCC, including family history, tumor size, metastasis and stage. Conversely, a negative association was revealed between the expression level of caspase-8 and clinicopathological features of patients with ESCC. Moreover, mRNA expression levels of EPHB4 and EFNB2 were negatively associated with survival times of patients with ESCC, whereas the level of caspase-8 was positively associated with patient outcome. The results from the present study suggested that EPHB4, EFNB2 and caspase-8 may be implicated in the tumorigenesis and progression of ESCC, and that consequently, they may serve as useful prognostic markers, as well as potential therapeutic targets.

Keywords: EFNB2; EPHB4; caspase-8; esophageal squamous cell cancer.