J Cancer 2020; 11(10):2778-2787. doi:10.7150/jca.38098

Research Paper

EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness

Jie Yin1,2, Zhilei Li3, Lin Ye2, Emily Birkin2, Liting Li2,4, Rui Xu5, Guangyong Chen5, Jiafu Ji4, Zhongtao Zhang1, Wen G. Jiang2, Yuxin Cui2✉

1. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Cancer Invasion and Metastasis Research and National Clinical Research Center for Digestive Diseases, 95 Yong-an Road, Xi-Cheng District, Beijing 100050, P.R. China
2. Cardiff China Medical Research Collaborative, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK
3. Department of Pharmacy, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, P.R. China
4. Key Laboratory of Carcinogenesis and Translational Research (Chinese Ministry of Education), Department of GI Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
5. Department of Pathology, Beijing Friendship Hospital, Capital Medical University;95 Yong-an Road, Xi-Cheng District, Beijing 100050, P.R. China

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Yin J, Li Z, Ye L, Birkin E, Li L, Xu R, Chen G, Ji J, Zhang Z, Jiang WG, Cui Y. EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness. J Cancer 2020; 11(10):2778-2787. doi:10.7150/jca.38098. Available from http://www.jcancer.org/v11p2778.htm

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Dysregulated expression of ephrin type-B receptor 2 (EphB2) has been linked with the development and progression of solid tumours. In the current study, we attempted to investigate the clinical relevance in GC and the effect of EphB2 expression on gastric cancer (GC) cells. EphB2 protein levels in GC and benign gastric tissues were determined using immunohistochemistry. EphB2 transcript expression in a GC cohort with GC tissue samples (n=171) and paired adjacent normal gastric tissues (n=97) was determined using qPCR. The EphB2 expression was over-activated using a CRISPR activator for the investigation of its cellular function. The expression levels of the EphB2 protein in the tumour tissues of tissue arrays were higher than the benign non-cancerous gastric tissues (P<0.05). EphB2 mRNA expression in GC tissues was also significantly elevated when compared with adjacent non-cancerous tissues (P<0.01). EphB2 activation promoted the migration and invasion abilities of the GC cell lines (P<0.01, respectively). In contrast, EphB2 activation significantly decreased the adhesion in GC cells (P<0.0001, respectively). The enrichment analysis of the correlated genes in a GC cohort indicates that EphB2 may function through mediating the cytokine-cytokine interaction, JAK-STAT and TP53 signaling pathways. In conclusion, EphB2 represents as a novel independent prognostic marker in GC. And activation of the EphB2 gene expression elevated the levels of migration and invasion, but suppressed adhesion of GC cells, indicating that EphB2 may act as a tumour promotor in GC. Our findings thus provide fundamental evidence for the consideration of the therapeutic potential of targeting EphB2 in GC.

Keywords: EphB2, gastric cancer, survival, aggressiveness