Guo Kai, Wang Tianbing, Yin Jimin, Yang Shoushan, Cui Haodong, Cao Zichuan, Zhao Qiang, Xie Gongbo, Lu Jian, Gu Guosheng, Wu Wenyong
Department of General Surgery, Anhui No.2 Provincial People's Hospital, Hefei, China.
Anhui No.2 Provincial People's Hospital Clinical College of Anhui Medical University, Hefei, China.
J Cell Mol Med. 2024 Dec;28(23):e70224. doi: 10.1111/jcmm.70224.
A novel copper-dependent mode of death, cuproptosis, has been newly identified. This study developed a cuproptosis score (CS) based on the cuproptosis model to analyse the association of CS with prognosis, immune cell infiltration, drug sensitivity and immunotherapy response in hepatocellular carcinoma (HCC) patients. A typing model of cuproptosis was constructed based on the expression of 19 cuproptosis-related genes (CRGs). A total of 485 samples were divided into high scoring group (HSG) and low scoring group (LSG) according to CS, and the drug sensitivity and responsiveness to immunotherapy were evaluated by combining the immunophenotype score (IPS), oncoPredict, the tumour immune dysfunction and rejection (TIDE). The use of weighted gene coexpression network analysis (WGCNA) identified key prognostic genes for cuproptosis. Western blotting was used to detect the expression level of the key gene. The CRG key gene glutaminase (GLS) is highly expressed in HCC, and patients with high expression of GLS have a poorer prognosis. Furthermore, cell function experiments, such as proliferation, migration and invasion assays, confirmed that GLS knockdown significantly changed the incidence and progression of HCC. This study suggests that new biological markers associated with cuproptosis can be used in the clinical diagnosis of HCC patients to predict prognosis and therapeutic targets.
一种新的铜依赖性死亡方式——铜死亡，已被新发现。本研究基于铜死亡模型开发了一种铜死亡评分（CS），以分析CS与肝细胞癌（HCC）患者预后、免疫细胞浸润、药物敏感性和免疫治疗反应之间的关联。基于19个铜死亡相关基因（CRG）的表达构建了铜死亡分型模型。根据CS将485个样本分为高分组（HSG）和低分组（LSG），并结合免疫表型评分（IPS）、肿瘤预测、肿瘤免疫功能障碍和排斥反应（TIDE）评估药物敏感性和对免疫治疗的反应性。使用加权基因共表达网络分析（WGCNA）确定了铜死亡的关键预后基因。采用蛋白质免疫印迹法检测关键基因的表达水平。CRG关键基因谷氨酰胺酶（GLS）在HCC中高表达，GLS高表达的患者预后较差。此外，细胞功能实验，如增殖、迁移和侵袭实验，证实敲低GLS可显著改变HCC的发生和进展。本研究表明，与铜死亡相关的新生物标志物可用于HCC患者的临床诊断，以预测预后和治疗靶点。
