Epithelial-mesenchymal transition (EMT) is a crucial mechanism that facilitates cancer cell metastasis. Despite its importance, the clinical significance of EMT in gastric cancer (GC) patients has yet to be clearly demonstrated. For gauging the extent of EMT in GC, we employed gene set variation analysis to score 807 patient samples from two large cohorts: TCGA and GSE84437. In both cohorts, EMT high GC showed a significant association with worse overall survival (hazard ratio (HR) = 1.74, p = 0.011 and HR = 2.01, p < 0.001, respectively). This association was stronger when considering the EMT signature score compared to the individual expressions of EMT-related genes (CDH1, CDH2, VIM, and FN1). While the EMT signature level did not differ among various cancers, high EMT signature specifically correlated with survival in GC alone. Mucinous and diffuse histological types exhibited higher EMT levels compared to others (p < 0.001), and the EMT signature level was correlated with tumor depth and AJCC stage (all p < 0.001). Interestingly, the EMT score was an independent factor for overall and disease-specific survival (multivariate; p = 0.006 and 0.032, respectively). EMT high GC displayed a lower fraction of Th1 cells and a higher fraction of dendritic cells, M1 macrophages and several stromal cells. EMT high GC exhibited an inverse correlation with cell proliferation-related gene sets. While they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis. The presence of EMT signature in a bulk tumor was linked to TGF-β signaling, hypoxia, and angiogenesis, and was also associated with poorer survival outcomes in GC patients.

上皮间质转化（EMT）是促进癌细胞转移的重要机制。尽管 EMT 很重要，但其在胃癌 (GC) 患者中的临床意义尚未得到明确证实。为了衡量 GC 中 EMT 的程度，我们采用基因集变异分析对来自两个大队列的 807 名患者样本进行评分：TCGA 和 GSE84437。在两个队列中，EMT 高 GC 显示与较差的总生存率显着相关（分别为风险比 (HR) = 1.74，p  = 0.011 和 HR = 2.01，p  < 0.001）。与 EMT 相关基因（CDH1、CDH2、VIM 和 FN1）的个体表达相比，考虑 EMT 特征评分时，这种关联性更强。虽然各种癌症之间的 EMT 特征水平没有差异，但高 EMT 特征与单独 GC 的生存率特别相关。与其他组织学类型相比，粘液性和弥漫性组织学类型表现出更高的 EMT 水平 ( p  < 0.001)，并且 EMT 特征水平与肿瘤深度和 AJCC 分期相关（均p  < 0.001）。有趣的是，EMT 评分是总体生存率和疾病特异性生存率的独立因素（多变量；p 分别为 0.006 和 0.032）。 EMT 高GC 显示出较低比例的Th1 细胞和较高比例的树突状细胞、M1 巨噬细胞和几种基质细胞。 EMT 高 GC 与细胞增殖相关基因组呈负相关。同时它们显着丰富了多种促癌基因集，例如 TGF-β 信号传导、缺氧和血管生成。大块肿瘤中 EMT 特征的存在与 TGF-β 信号传导、缺氧和血管生成有关，并且还与 GC 患者较差的生存结果相关。