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Receptor Tyrosine Kinase EphB3: a Prognostic Indicator in Colorectal Carcinoma

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Pathology & Oncology Research

Abstract

Although EphB3 expression is down-regulated in colorectal cancer (CRC) cells compared with normal intestinal epithelial cells, the relationship between EphB3 expression and clinicopathological parameters in CRC is unclear. We examined EphB3 expression in 128 CRC tissue specimens and in 19 adenoma specimens using immunohistochemistry. The relationships between EphB3 expression and clinicopathological parameters, KRAS mutations, BRAF V600E mutation, MSI and survival were evaluated using Spearman’s rank correlation and Kaplan–Meier survival analyses, respectively. CpG methylation in the EphB3 promoter was examined in four human CRC cell lines and tissues. EphB3 was strongly expressed in all normal intestinal epithelial cells (128/128) and adenoma cells (19/19). In CRC tumor cells, EphB3 expression was negative or weak in 41.4% (53/128), moderate in 26.6% (34/128), and strong in 32.0% (41/128) of samples. EphB3 expression was negatively associated with invasive depth (P = 0.016, rs = −0.213), lymph node metastasis (P = 0.000, rs = −0.490), and TNM stage (P = 0.000, rs = −0.390), and was positively associated with poor differentiation (P = 0.001, rs = 0.290), BRAF V600E mutation (P = 0.008, rs = 0.235), and longer overall survival (P < 0.001). In multivariate analysis, EphB3 expression (P = 0.007) and lymph node metastasis (P < 0.001) were independent prognostic factors for poor survival. Hypermethylation of the EphB3 promoter was detected in cell lines and CRC tissues. EphB3 is down-regulated in CRC compared to normal mucosa. Hypermethylation of CpG island is contributed to downregulation of EphB3 in CRC. EphB3 expression in tumor cells may be a useful prognostic indicator for patients with CRC.

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Acknowledgements

The authors wish to thank the patients who participate in this study. This study was supported by grants from the National Basic Research Priorities Program 973 Project (2014CB744504) from the Ministry of Science and Technology of China and the National Natural Science Foundation of China (81371611).

We thank Anne M. O’Rourke, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

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Authors and Affiliations

  1. Department of Colorectal Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

    Zhuoqi Xuan, Yong Wang & Yueming Sun

  2. Department of Gastrointestinal Surgery, the Jiangyin People’s Hospital, Jinagsu, 214400, China

    Zhuoqi Xuan, Jianming Huang & Lin Gao

  3. Department of Pathology, Jinling Hospital, Nanjing University School of Medicine, No.305, Zhong San Dong Lu, Nanjing, 210002, China

    Jiandong Wang

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  1. Zhuoqi Xuan
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Xuan, Z., Huang, J., Gao, L. et al. Receptor Tyrosine Kinase EphB3: a Prognostic Indicator in Colorectal Carcinoma. Pathol. Oncol. Res. 26, 541–549 (2020). https://doi.org/10.1007/s12253-018-0562-x

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