skip to main content
Show Results with:

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

Gastric Cancer, 2015, Vol.18(3), pp.485-494 [Peer Reviewed Journal]

Full text available

  • Title:
    Overexpression of Ephrin A2 receptors in cancer stromal cells is a prognostic factor for the relapse of gastric cancer
  • Author: Kikuchi, Shojiro ; Kaibe, Nobuaki ; Morimoto, Koji ; Fukui, Hirokazu ; Niwa, Hirotaka ; Maeyama, Yoshihiro ; Takemura, Masashi ; Matsumoto, Masaki ; Nakamori, Shoji ; Miwa, Hiroto ; Hirota, Seiichi ; Sasako, Mitsuru
  • Found In: Gastric Cancer, 2015, Vol.18(3), pp.485-494 [Peer Reviewed Journal]
  • Subjects: EphA2 ; Gastric cancer ; Stromal reaction ; Predictive marker ; Cancer-associated fibroblasts
  • Language: English
  • Description: Byline: Shojiro Kikuchi (1), Nobuaki Kaibe (1), Koji Morimoto (2), Hirokazu Fukui (3), Hirotaka Niwa (1), Yoshihiro Maeyama (1), Masashi Takemura (1), Masaki Matsumoto (4), Shoji Nakamori (5), Hiroto Miwa (3), Seiichi Hirota (6), Mitsuru Sasako (1) Keywords: EphA2; Gastric cancer; Stromal reaction; Predictive marker; Cancer-associated fibroblasts 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 a[yen]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. Author Affiliation: (1) Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan (2) Department of Breast and Endocrine Surgery, Osaka University, Osaka, Japan (3) Department of Medicine, Hyogo College of Medicine, Nishinomiya, Japan (4) Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan (5) Department of Surgery, Osaka National Hospital, Osaka, Japan (6) Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan Article History: Registration Date: 22/05/2014 Received Date: 06/02/2014 Accepted Date: 15/05/2014 Online Date: 08/06/2014 Article note: S. Kikuchi and N. Kaibe contributed equally to this work. Electronic supplementary material The online version of this article (doi: 10.1007/s10120-014-0390-y) contains supplementary material, which is available to authorized users.
  • Identifier: ISSN: 1436-3291 ; E-ISSN: 1436-3305 ; DOI: 10.1007/s10120-014-0390-y

Searching Remote Databases, Please Wait