Li Xinqiang, Jiang Peng, Li Ruixia, Wu Bin, Zhao Kai, Li Shipeng, Cai Jinzhen
Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China.
Institute of Organ Donation and Transplantation, Medical College of Qingdao University, Qingdao, China.
Front Oncol. 2022 Nov 2;12:1009036. doi: 10.3389/fonc.2022.1009036. eCollection 2022.
Cuproptosis represents a novel copper-dependent regulated cell death, distinct from other known cell death processes. In this report, a comprehensive analysis of cuproptosis in hepatocellular carcinoma (HCC) was conducted using multi-omics including genomics, bulk RNA-seq, single cell RNA-seq and proteomics. ATP7A, PDHA1 and DLST comprised the top 3 mutation genes in The Cancer Genome Atlas (TCGA)-LIHC; 9 cuproptosis-related genes showed significant, independent prognostic values. Cuproptosis-related hepatocytes were identified and their function were evaluated in single cell assays. Based on cuproptosis-related gene expressions, two immune patterns were found, with the cuproptosis-C1 subtype identified as a cytotoxic immune pattern, while the cuproptosis-C2 subtype was identified as a regulatory immune pattern. Cuproptosis-C2 was associated with a number of pathways involving tumorigenesis. A prognosis model based on differentially expressed genes (DEGs) of cuproptosis patterns was constructed and validated. We established a cuproptosis index (CPI) and further performed an analysis of its clinical relevance. High CPI values were associated with increased levels of alpha-fetoprotein (AFP) and advanced tumor stages. Taken together, this comprehensive analysis provides important, new insights into cuproptosis mechanisms associated with human HCC.
铜死亡是一种新型的铜依赖性调控细胞死亡，与其他已知的细胞死亡过程不同。在本报告中，我们使用包括基因组学、批量RNA测序、单细胞RNA测序和蛋白质组学在内的多组学技术对肝细胞癌（HCC）中的铜死亡进行了全面分析。ATP7A、PDHA1和DLST是癌症基因组图谱（TCGA）-LIHC中排名前三的突变基因；9个与铜死亡相关的基因显示出显著的、独立的预后价值。在单细胞分析中鉴定了与铜死亡相关的肝细胞并评估了其功能。基于与铜死亡相关的基因表达，发现了两种免疫模式，其中铜死亡-C1亚型被鉴定为细胞毒性免疫模式，而铜死亡-C2亚型被鉴定为调节性免疫模式。铜死亡-C2与许多涉及肿瘤发生的途径相关。构建并验证了基于铜死亡模式差异表达基因（DEG）的预后模型。我们建立了铜死亡指数（CPI）并进一步分析了其临床相关性。高CPI值与甲胎蛋白（AFP）水平升高和肿瘤晚期相关。综上所述，这一全面分析为与人类HCC相关的铜死亡机制提供了重要的新见解。
