Wang Ke-Wei, Wang Mei-Dan, Li Zi-Xi, Hu Ben-Shun, Huang Jian-Feng, Wu Jun-Jie, Yuan Zheng-Dong, Wu Xiao-Long, Yuan Qin-Fang, Sun Yi-Fan, Yuan Feng-Lai
Institute of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Jiangnan University, Wuxi, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China.
Heliyon. 2023 Feb 17;9(3):e13831. doi: 10.1016/j.heliyon.2023.e13831. eCollection 2023 Mar.
Cuprotosis is a new programmed cell death related to cancer. However, the characteristics of cuprotosis in gastric cancer (GC) remain unknown. Ten cuprotosis molecules from 1544 GC patients were used to identify three GC molecular genotypes. Cluster A was characterized by the best clinical outcome and was significantly enriched in metabolic signaling pathways. Cluster B exhibited elevated immune activation, high immune stroma scores and was significantly enriched in tumor immune signaling pathways. Cluster C was characterized by severe immunosuppression and poor response to immunotherapy. Notably, the citrate cycle, cell cycle, and p53 signaling pathways were enriched in the differentially expressed genes among the three subtypes, which were critical signaling pathways for cell death. We also developed a cuprotosis signature risk score that could accurately predict the survival, immunity, and subtype of GC. This study presents a systematic analysis of cuprotosis molecules and provides new immunotherapeutic targets for GC patients.
铜死亡是一种与癌症相关的新型程序性细胞死亡。然而，胃癌（GC）中铜死亡的特征仍不清楚。利用1544名GC患者的10个铜死亡分子来确定三种GC分子基因型。A组的特征是临床结果最佳，并且在代谢信号通路中显著富集。B组表现出免疫激活增强、免疫基质评分高，并且在肿瘤免疫信号通路中显著富集。C组的特征是严重免疫抑制和对免疫治疗反应不佳。值得注意的是，柠檬酸循环、细胞周期和p53信号通路在三种亚型的差异表达基因中富集，这些是细胞死亡的关键信号通路。我们还开发了一种铜死亡特征风险评分，可准确预测GC患者的生存、免疫和亚型。本研究对铜死亡分子进行了系统分析，并为GC患者提供了新的免疫治疗靶点。
