Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE

Kenichiro Furukawa, Keiichi Hatakeyama, Masanori Terashima, Takeshi Nagashima, Kenichi Urakami, Keiichi Ohshima, Akifumi Notsu, Takashi Sugino, Taisuke Yagi, Keiichi Fujiya, Satoshi Kamiya, Makoto Hikage, Yutaka Tanizawa, Etsuro Bando, Yae Kanai, Yasuto Akiyama, Ken Yamaguchi

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Background: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. Methods: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). Results: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. Conclusions: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.

本文言語English
ページ(範囲)138-148
ページ数11
ジャーナルGastric Cancer
25
1
DOI
出版ステータスPublished - 2022 1月

ASJC Scopus subject areas

  • 腫瘍学
  • 消化器病学
  • 癌研究

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