Gastric Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 7, 2008; 14(37): 5650-5656
Published online Oct 7, 2008. doi: 10.3748/wjg.14.5650
Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers
Mariko Oki, Hiroyuki Yamamoto, Hiroaki Taniguchi, Yasushi Adachi, Kohzoh Imai, Yasuhisa Shinomura
Mariko Oki, Hiroyuki Yamamoto, Hiroaki Taniguchi, Yasushi Adachi, Yasuhisa Shinomura, First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
Kohzoh Imai, Sapporo Medical University, Sapporo 060-8556, Japan
Author contributions: Oki M and Yamamoto H contributed equally to this paper and designed research; Oki M, Yamamoto H, Taniguchi H, and Adachi Y performed research; Oki M, Taniguchi H, Yamamoto H, Imai K, and Shinomura Y analyzed data; and Oki M, Yamamoto H, and Shinomura Y wrote the paper.
Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (H.Y. and K.I.) and Grants-in-Aid for Cancer Research and for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan (H.Y. and K.I.)
Correspondence to: Hiroyuki Yamamoto, MD, FJSIM, PhD, First Department of Internal Medicine, Sapporo Medical University, S.-1, W.-16, Chuo-ku, Sapporo 060-8543, Japan.
Telephone: +81-11-6112111 Fax: +81-11-6112282
Received: March 28, 2008
Revised: August 26, 2008
Accepted: September 2, 2008
Published online: October 7, 2008

AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands.

METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed.

RESULTS: Overexpression of EphA4 mRNA expression was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Overexpression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth.

CONCLUSION: Our results suggest that overexpression of EphA4 plays a role in gastric cancer.

Keywords: Ephrin receptor A4, Gastric cancer, Ephrin, Fibroblast growth factor receptor 1, Prognosis