TY - JOUR
T1 - Overexpression of Ephrin A2 receptors in cancer stromal cells is a prognostic factor for the relapse of gastric cancer
AU - Kikuchi, Shojiro
AU - Kaibe, Nobuaki
AU - Morimoto, Koji
AU - Fukui, Hirokazu
AU - Niwa, Hirotaka
AU - Maeyama, Yoshihiro
AU - Takemura, Masashi
AU - Matsumoto, Masaki
AU - Nakamori, Shoji
AU - Miwa, Hiroto
AU - Hirota, Seiichi
AU - Sasako, Mitsuru
N1 - Funding Information:
The authors thank Prof. Kenji Nakanishi, who provided continuing support and constant encouragement throughout this project. We also thank Yuko Yasui of the Department of Surgery, and Nobuyuki Adachi and Ryota Shinozaki of the HCM Joint-Use Research facilities for technical contributions. This work was supported in part by a Grant-in-Aid for Scientific Research (C) 25460466, Grant-in-Aid for Researchers, Hyogo College of Medicine, 2012, to Shojiro Kikuchi; a Ministry of Education, Culture, Sports, Science and Technology of Japan—Supported Program for the Strategic Research Foundation at Private Universities, 2012–2015 and a Grant-in-Aid for Scientific Research (C) 23591949 to Mitsuru Sasako; and a grant from the Third-Term Comprehensive Control Research for Cancer conducted by the Ministry of Health, Labour and Welfare of Japan, and Charitable Trust Laboratory Medicine Foundation of Japan to Mitsuru Sasako.
Publisher Copyright:
© 2014, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
PY - 2015/7/27
Y1 - 2015/7/27
N2 - 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.
AB - 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.
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U2 - 10.1007/s10120-014-0390-y
DO - 10.1007/s10120-014-0390-y
M3 - Article
C2 - 24908114
AN - SCOPUS:84938978291
SN - 1436-3291
VL - 18
SP - 485
EP - 494
JO - Gastric Cancer
JF - Gastric Cancer
IS - 3
ER -
