MAGEA10 expression is a predictive marker of early hepatic recurrence after curative gastrectomy for gastric and gastroe
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ORIGINAL ARTICLE
MAGEA10 expression is a predictive marker of early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer Keiichi Fujiya1,2 · Masanori Terashima1 · Keiichi Ohshima3 · Daisuke Aizawa4 · Takashi Sugino4 · Masakuni Serizawa5 · Kenichi Nakamura1 · Takeshi Nagashima6,7 · Keiichi Hatakeyama3 · Kenichi Urakami6 · Yasuto Akiyama8 · Yasuhiro Tsubosa9 · Yuko Kitagawa2 · Ken Yamaguchi10 Received: 9 July 2020 / Accepted: 12 September 2020 © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2020
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. Keywords Gene expression profiling · Comprehensive analysis · MAGEA family
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10120-020-01123-y) contains supplementary material, which is available to authorized users. * Masanori Terashima [email protected] 1
Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi‑cho, Sunto‑gun, Shizuoka 411‑8777, Japan
5
Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
6
Cancer Diagnostics Research Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan
7
SRL, Inc., Tokyo, Japan
2
Department of Sur
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