Lin Shitong, Xu Yashi, Liu Binghan, Zheng Lingling, Cao Canhui, Wu Peng, Ding Wencheng, Ren Fang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei, 430022, China.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Heliyon. 2023 Mar 16;9(4):e14613. doi: 10.1016/j.heliyon.2023.e14613. eCollection 2023 Apr.
Cuproptosis is a copper-dependent model of cell death involved in tumor genesis and progression. Its roles in uterine corpus endometrial carcinoma (UCEC) remains elusive. Here, we aimed to explore the expression and prognostic values of cuprotosis-related genes (CRGs) in UCEC. Expression profiles and clinical data of UCEC were downloaded from The Cancer Genome Atlas (TCGA), and randomly divided into testing or training cohort (1:1 ratio). The CRG signature was identified by LASSO regression analysis. The differentially expressed genes and their functional enrichment analysis were performed by the "limma" R package and Metascape, respectively. The immunocytes infiltration was measured by TIMER, and "GSVA" R package. In total, seven differentially expressed prognostic genes of CRGs in UCEC were identified, and four genes (, , , and ) were selected to construct a predictive model in training cohort. UCEC patients from training and testing cohorts were further divided into high- or low-risk groups according to the median risk score. High-risk group favored poor prognosis compared to low-risk group. Functional enrichment analysis revealed this CRG signature were got involved in the process of cell-cell adhesion and immune activities (e.g., IL-1 signaling pathway, cellular response to cytokine stimulus). Further analyses revealed there were significant differences between high- and low-risk patients regarding immunocytes infiltration, chemokines, and chemokine receptors. Finally, the expression and biological functions of identified CRGs were confirmed by UCEC samples and experimental methods . In summary, the CRG signature was significantly correlated with patients' overall survival, which could provide insights into the diagnosis and prognosis prediction for UCEC.
铜死亡是一种依赖铜的细胞死亡模式,参与肿瘤的发生和发展。其在子宫内膜癌(UCEC)中的作用仍不清楚。在此,我们旨在探讨UCEC中铜死亡相关基因(CRGs)的表达及预后价值。从癌症基因组图谱(TCGA)下载UCEC的表达谱和临床数据,并随机分为测试或训练队列(1:1比例)。通过LASSO回归分析确定CRG特征。分别使用“limma”R包和Metascape进行差异表达基因及其功能富集分析。通过TIMER和“GSVA”R包测量免疫细胞浸润。总共鉴定出UCEC中CRGs的7个差异表达的预后基因,并选择4个基因(、、、和)在训练队列中构建预测模型。根据中位风险评分,将来自训练和测试队列的UCEC患者进一步分为高风险或低风险组。与低风险组相比,高风险组预后较差。功能富集分析显示,该CRG特征参与细胞间粘附和免疫活动过程(如IL-1信号通路、细胞对细胞因子刺激的反应)。进一步分析显示,高风险和低风险患者在免疫细胞浸润、趋化因子和趋化因子受体方面存在显著差异。最后,通过UCEC样本和实验方法证实了所鉴定的CRGs的表达和生物学功能。总之,CRG特征与患者的总生存期显著相关,可为UCEC的诊断和预后预测提供见解。