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

Yin, Jie, Li, Zhilei, Ye, Lin, Birkin, Emily, Li, Liting, Xu, Rui, Chen, Guangyong, Ji, Jiafu, Zhang, Zhongtao, Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111 and Cui, Yuxin 2020. EphB2 represents an independent prognostic marker in patients with gastric cancer and promotes tumour cell aggressiveness. Journal of Cancer 11 (10) , pp. 2778-2787. 10.7150/jca.38098

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Abstract

Dysregulated expression of ephrin type-B receptor 2 (EphB2) has been linked with 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Ivyspring International Publisher
ISSN:	1837-9664
Funders:	National Natural Science Foundation of China (81541050 and 81641109), National Key Technologies R&D Program (2015BAI13B09), Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201504), Beijing Municipal Administration of Hospitals? Youth Program (QML20160105), CCMRC and Cancer Research Wales.
Date of First Compliant Deposit:	17 February 2020
Date of Acceptance:	19 January 2020
Last Modified:	05 May 2023 12:41
URI:	https://orca.cardiff.ac.uk/id/eprint/129685

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