Keiichi Fujiya1,2, Masanori Terashima3, Keiichi Ohshima4, Daisuke Aizawa5, Takashi Sugino5, Masakuni Serizawa6, Kenichi Nakamura1, Takeshi Nagashima7,8, Keiichi Hatakeyama4, Kenichi Urakami7, Yasuto Akiyama9, Yasuhiro Tsubosa10, Yuko Kitagawa2, Ken Yamaguchi11. 1. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 2. Department of Surgery, Keio University School of Medicine, Tokyo, Japan. 3. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. m.terashima@scchr.jp. 4. Medical Genetics Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 5. Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan. 6. Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 7. Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 8. SRL, Inc., Tokyo, Japan. 9. Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. 10. Division of Esophageal Surgery, Shizuoka Cancer Center, Shizuoka, Japan. 11. Shizuoka Cancer Center, Shizuoka, Japan.
Abstract
BACKGROUND: Resection for hepatic recurrence after gastrectomy in patients with gastric cancer may be curative; however, the prediction of hepatic recurrence remains intractable. Therefore, we aimed to explore predictive markers for hepatic recurrence in gastric and gastroesophageal junction cancer based on genetic information. METHODS: This study recruited 154 patients who underwent curative gastrectomy for pathological stage II or III primary gastric and gastroesophageal junction adenocarcinoma. Genes associated with hepatic recurrence were comprehensively analyzed using whole-exome sequencing and gene expression profiling (GEP), followed by immunohistochemistry analysis for MAGEA10. The cumulative incidences of hepatic recurrence, relapse-free survival, and overall survival were evaluated. RESULTS: A total of 12 patients with early hepatic recurrences were found within 2 years of surgery. Although there were no distinct gene mutations in recurrent patients, upregulation of MAGEA10 was identified in patients with early hepatic recurrence using GEP analysis. Immunostaining for MAGEA10 stained the cell nuclei in 29 (18.8%) of 154 samples. Furthermore, protein expression of MAGEA10 on immunohistochemistry was significantly related to a high MAGEA10 mRNA expression, high cumulative incidences of hepatic recurrence, and poor relapse-free survival. Overall survival did not differ significantly between positive and negative immunohistochemical staining for MAGEA10. The sensitivity and specificity of MAGEA10 staining for early hepatic recurrence were 58.3% and 84.5%, respectively. CONCLUSIONS: MAGEA10 represents a promising predictive marker for early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.
BACKGROUND: Resection for hepatic recurrence after gastrectomy in patients with gastric cancer may be curative; however, the prediction of hepatic recurrence remains intractable. Therefore, we aimed to explore predictive markers for hepatic recurrence in gastric and gastroesophageal junction cancer based on genetic information. METHODS: This study recruited 154 patients who underwent curative gastrectomy for pathological stage II or III primary gastric and gastroesophageal junction adenocarcinoma. Genes associated with hepatic recurrence were comprehensively analyzed using whole-exome sequencing and gene expression profiling (GEP), followed by immunohistochemistry analysis for MAGEA10. The cumulative incidences of hepatic recurrence, relapse-free survival, and overall survival were evaluated. RESULTS: A total of 12 patients with early hepatic recurrences were found within 2 years of surgery. Although there were no distinct gene mutations in recurrent patients, upregulation of MAGEA10 was identified in patients with early hepatic recurrence using GEP analysis. Immunostaining for MAGEA10 stained the cell nuclei in 29 (18.8%) of 154 samples. Furthermore, protein expression of MAGEA10 on immunohistochemistry was significantly related to a high MAGEA10 mRNA expression, high cumulative incidences of hepatic recurrence, and poor relapse-free survival. Overall survival did not differ significantly between positive and negative immunohistochemical staining for MAGEA10. The sensitivity and specificity of MAGEA10 staining for early hepatic recurrence were 58.3% and 84.5%, respectively. CONCLUSIONS: MAGEA10 represents a promising predictive marker for early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.
Entities:
Keywords:
Comprehensive analysis; Gene expression profiling; MAGEA family
Authors: Eun Ji Jung; Min A Kim; Hye Seung Lee; Han Kwang Yang; You Mie Lee; Byung Lan Lee; Woo Ho Kim Journal: Anticancer Res Date: 2005 May-Jun Impact factor: 2.480