Identification of Cuproptosis‐Related Patterns Predict Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

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.