Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE
Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE
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DOI：
10.1007/s10120-021-01242-0
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发表时间：
2021-09-02
期刊：
影响因子：
7.4
通讯作者：
Yamaguchi, Ken
中科院分区：
文献类型：
--
作者：
Furukawa, Kenichiro;Hatakeyama, Keiichi;Yamaguchi, Ken
背景胃癌（GC）的分类是基于分子图谱，如癌症基因组图谱（TCGA）和亚洲癌症研究组（ACRG），并试图建立基于这些分类的治疗策略。然而，根据这些分类很难预测生存，特别是在根治性切除的患者。我们的目的是建立一个新的胃癌分子分类，预测患者接受根治性胃切除术的生存。方法本研究包括499例日本晚期胃癌患者行根治性（R0/R1）胃切除术。进行了全外显子组测序、面板测序和基因表达谱分析（基于高科技Omics-based Patient Evaluation [Project HOPE]）。我们根据TCGA和ACRG亚型对患者进行分类，并评估临床病理特征和生存率。然后，我们尝试根据与生物学特征和生存相关的分子谱对患者进行分类（HOPE分类）。结果TCGA和ACRG分型均不能预测患者的生存率。在HOPE分类中，首先选择高突变（HMT）肿瘤作为区别特征，然后提取T细胞炎症表达特征高（TCI）肿瘤。最后，剩余的肿瘤通过上皮-间质转化（EMT）表达特征来划分。HOPE分级显著预测了疾病特异性生存率和总生存率（分别为p <0.001和0.020）。HMT + TCI组生存率最高，而EMT-高组生存率最差。在TCGA队列中成功验证了HOPE分类。结论我们建立了一个新的胃癌分子分类，可以预测接受根治性手术的患者的生存率。
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.