Combining immunogenic cell death and cuproptosis to construct a prognostic signature and predict the immune status and treatment efficacy for hepatocellular carcinoma

Abstract Background Immunogenic cell death (ICD) is defined as cell death sufficient to activate an adaptive immune response in an immunocompetent host. Cuproptosis is induced by increased intracellular toxicity due to copper ion accumulation. ICD and cuproptosis have great potential in regulating the growth and proliferation of cancer cells. Methods We used transcriptome data from TCGA database to identify two subtypes based on consensus clustering and explored the differences between the two groups. We further combined ICD- and cuproptosis-related genes to develop a signature and predict OS, immune status, and treatment responses in HCC patients. An ICGC cohort was used for external validation. Results Patients in the groups with high expression of ICD- and cuproptosis-related genes had higher levels of immune cell infiltration and a better immunotherapeutic response. Eight related genes (BAX, HSP90AA1, IFNB1, LY96, NT5E, LIPT1, DLAT, and CDKN2A) were screened for the prognostic signature. The survival analysis revealed that patients in the low-risk group were less likely to die at an early stage than were those in the high-risk group. The signature also showed better results in predicting immune cell infiltration and the treatment response. Conclusions Our study revealed that the prognostic signature constructed by combining ICD- and cuproptosis-related genes performs well in predicting the survival of patients with HCC and is closely associated with immune cell infiltration and immunotherapy.