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Gastric Cancer
Published in: Gastric Cancer 3/2015

01-07-2015 | Original Article

Overexpression of Ephrin A2 receptors in cancer stromal cells is a prognostic factor for the relapse of gastric cancer

Authors: Shojiro Kikuchi, Nobuaki Kaibe, Koji Morimoto, Hirokazu Fukui, Hirotaka Niwa, Yoshihiro Maeyama, Masashi Takemura, Masaki Matsumoto, Shoji Nakamori, Hiroto Miwa, Seiichi Hirota, Mitsuru Sasako

Published in: Gastric Cancer | Issue 3/2015

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Abstract

Background

Microenvironments control cancer growth and progression. We explored the prognostic impact of stromal reaction and cancer stromal cells on relapse risk and survival after curative gastrectomy in gastric cancer patients.

Methods

Tissue samples were obtained from 107 patients with gastric adenocarcinoma who underwent curative (R0) gastrectomy. Primary stromal cells isolated from gastric cancer tissue (GCSC) and normal gastric tissue (Gastric stromal cell: GSC) in each patient were cultured and subjected to comprehensive proteome (LC–MS/MS) and real-time RT-PCR analysis. Expression of Ephrin A2 receptors (EphA2) in cancers and GCSC was evaluated immunohistochemically. Intermingling of EphA2-positive cancer cells and GCSC (IC/A2+) and overexpression of EphA2 in cancer cells (Ca/A2+) in invasive parts of tumors were assessed, as were relationships of IC/A2+, Ca/A2+, and clinicopathological factors with relapse-free survival and overall survival.

Results

Proteome analysis showed that EphA2 expression was significantly higher in GCSC than GSC. Real-time RT-PCR analysis showed that levels of EphA1/A2/A3/A5 and EphB2/B4 were ≥2.0-fold higher in GCSC than GSC. Ca/A2 and IC/A2 were positive in 65 (60.7 %) and 26 (24.3 %) patients, respectively. Relapse was significantly more frequent in IC/A2-positive than in IC/A2-negative (HR, 2.12; 95 % CI, 1.16–5.41; p = 0.0207) patients. Among the 54 patients who received S-1 adjuvant chemotherapy, relapse-free survival (RFS) was significantly shorter in those who were IC/A2-positive than in those who were IC/A2-negative and Ca/A2-negative (HR, 2.83; 95 % CI, 1.12–12.12; p = 0.0339). Multivariable analysis indicated that pathological stage (p = 0.010) and IC/A2+ (p = 0.008) were independent risk factors for recurrence.

Conclusion

IC/A2+ was predictive of relapse after curative (R0) gastrectomy.
Appendix
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Metadata
Title
Overexpression of Ephrin A2 receptors in cancer stromal cells is a prognostic factor for the relapse of gastric cancer
Authors
Shojiro Kikuchi
Nobuaki Kaibe
Koji Morimoto
Hirokazu Fukui
Hirotaka Niwa
Yoshihiro Maeyama
Masashi Takemura
Masaki Matsumoto
Shoji Nakamori
Hiroto Miwa
Seiichi Hirota
Mitsuru Sasako
Publication date
01-07-2015
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 3/2015
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-014-0390-y

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