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Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival

  • Original Article—Alimentary Tract
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Abstract

Background

EphA3, a member of the Eph receptor tyrosine kinases, plays important roles in tumor angiogenesis and progression. However, the function of EphA3 in solid tumors has not been widely studied. We aimed to explore EphA3 expression in gastric carcinoma and analyze its role as a potential prognostic factor.

Methods

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess EphA3 mRNA in a normal gastric mucosa cell line and carcinoma cell lines. Immunohistochemistry for EphA3 and vascular endothelial growth factor (VEGF) was performed in 318 cases of gastric carcinoma. CD34 immunohistochemical staining was used for microvessel density (MVD) counting. Western blotting was used to analyze EphA3 expression in the cell lines and to determine the expression of EphA3 and VEGF in 75 cases of gastric carcinoma and matched normal mucosa.

Results

EphA3 mRNA and protein expression was significantly higher in gastric cancer than that in normal mucosa (all P < 0.001). EphA3 was significantly correlated with TNM stage and poor prognosis (all P < 0.001). Multivariate analysis showed that EphA3 had an independent effect on survival (P = 0.037). EphA3 was positively correlated with VEGF (P < 0.001), and MVD (P < 0.001). According to Western blot analysis, both EphA3 and VEGF expression were significantly higher in carcinoma than that in normal mucosa (all P < 0.001). A positive correlation was observed between EphA3 and VEGF expression in cancer (P < 0.001, r = 0.513).

Conclusions

EphA3 may play important roles in the angiogenesis and prognosis of gastric carcinoma, and thus may become a useful target for therapeutic intervention and a potential indicator for clinical assessment of tumor prognosis.

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Abbreviations

B :

Partial regression coefficient

Ephs:

Eph receptors

HR:

Hazard ratio

MVD:

Microvessel density

PBS:

Phosphate-buffered saline

RTK:

Receptor tyrosine kinase

SE:

Standard error

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We thank Professor Po Zhao and Dr. Yazhuo Li, Department of Pathology, Chinese People’s Liberation Army General Hospital, for their excellent technical assistance. This work was supported by a Grant from the Committee of Science and Technology of Beijing, China, No. Z111107058811047.

Conflict of interest

No conflicts of interest exist.

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Authors and Affiliations

  1. Department of General Surgery, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Hong-Qing Xi, Xiao-Song Wu, Bo Wei & Lin Chen

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  1. Hong-Qing Xi
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  2. Xiao-Song Wu
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Corresponding author

Correspondence to Lin Chen.

Additional information

H.-Q. Xi and X.-S. Wu contributed equally to this work.

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Xi, HQ., Wu, XS., Wei, B. et al. Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival. J Gastroenterol 47, 785–794 (2012). https://doi.org/10.1007/s00535-012-0549-4

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  • DOI: https://doi.org/10.1007/s00535-012-0549-4

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