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Abstract Abstract: Cuproptosis is a new programmed cell death pathway, which is initiated by the direct binding of copper to the fatty acyl tricarboxylic acid cycle proteins. Modulation of cuproptosis in tumor cells is a novel therapeutic approach. However, the potential role and clinical significance of cuproptosis-related long non-coding RNA (lncRNA) in hepatocellular carcinoma (HCC) remain unclear. In this study, a total of 994 cuproptosis-related lncRNA were identified by co-expression analysis of 19 cuproptosis-related genes based on the TCGA-LIHC dataset. LASSO regression and multivariate Cox regression analysis were used to screen out four prognostic lncRNA (TMCC1-AS1, AC009974.2, AL355574.1 and DDX11-AS1) related to copper mortality to construct a prognostic risk model, and the risk scores of all HCC patient samples were calculated. HCC patients were divided into high risk and low risk groups at a 1:1 ratio. Kaplan-Meier survival curve analysis showed that the overall survival rate (OS) of the high risk group was significantly lower than that of the low risk group. Regression analysis and ROC curve confirmed the prognostic value of the risk score. In addition, we analyzed the correlation between risk scores and pathway enrichment analysis, immune checkpoint genes, immune cell infiltration, anticancer drug sensitivity, and somatic gene mutations. The results of differential expression analysis showed that TMCC1-AS1, AC009974.2, AL355574.1 and DDX11-AS1 were all up-regulated in tumor tissues, which were verified by real-time fluorescent quantitative PCR (qRT-PCR) in tumor tissues and adjacent liver tissues collected from 8 patients with hepatocellular carcinoma undergoing radical surgery. This give histological evidence for this model. In conclusion, a risk model composed of four cuproptosis-related lncRNA was constructed, which was significantly related to the prognosis and immune infiltration environment of patients. This model has certain clinical application value in predicting the effects of immunotherapy and guiding the selection of chemotherapy drugs.
Key words: hepatocellular carcinoma; cuproptosis; immune escape; tumor mutation burden; LncRNA
（Acta Laser Biology Sinica, 2023, 32(4): 330-344）
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