| Background:Copper death,a novel form of cell death,is associated with intracellular energy metabolism and mitochondria,and plays a role in cancer development.Long non-coding RNA(lncRNA)is associated with the progression and prognosis of hepatocellular carcinoma(HCC).However,the role and prognostic value of Cuproptosis-related lncRNAs in HCC have not been clarified.In this study,we constructed a prognostic model of Cuproptosis-related lncRNAs in HCC and evaluated the prognostic value of this model.Method:We downloaded mRNA and lncRNA expression profiles and corresponding clinical data of HCC from TCGA and obtained 832 Cuproptosis-related lncRNAs.Five Cuproptosis-related prognostic lncRNAs were constructed after univariate,least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression,and HCC was classified into high-and low-risk groups according to the model.Kaplan-Meier(KM)analysis,receiver operating characteristic(ROC)curve,C-index,independent prognostic analysis,nomogram and principal component analysis(PCA)were used to assess the predictive power of the prognostic models.The model was also explored for immune infiltration,immune blockade,drug sensitivity,and gene mutation.Finally,clinical prognosis and single-gene Gene Set Enrichment Analysis(GSEA)were performed for each of the five lncRNAs in the model.Result:The overall survival(OS),progression-free survival(PFS),disease-specific survival(DSS)and disease-free interval(DFI)were shorter in the high-risk group of hepatocellular carcinoma patients.The risk model had good predictive value for liver cancer in the training set,validation set and complete set,with the training set(1 year:AUC=0.762,3 years: ACU=0.725,5 years: AUC=0.772),validation set(1 year:AUC=0.732,3 years: ACU=0.653,5 years: AUC=0.590)and complete set(1 year:AUC= 0.752,3 years: ACU=0.701,5 years: AUC=0.682).We then discussed the risk model separately with clinical subgroups of hepatocellular carcinoma and found that the model had equally good predictive value in most clinical subgroup types.Univariate and multifactorial analyses of model risk and hepatocellular carcinoma clinical factors on prognostic resolution of hepatocellular carcinoma showed that in all three datasets,model risk independently predicted survival resolution of hepatocellular carcinoma in both univariate and multifactorial analyses.Nomogram and its calibration curves showed that inclusion of the model was able to better assess the overall prognosis of patients with hepatocellular carcinoma compared to non-inclusion of the risk model.Not only that,we also explored the association of the model with immunity in liver cancer,and we found that there were differences in immune cells(imc)and immune function(imf)between the high and low risk groups classified by the model,not only that there were also differences in immune checkpoints between the high and low risk groups of the model,which provided us with the immune mechanism of the model,but also illustrated the value of the model as immunotherapy from the side.For better clinical relevance,we also performed drug sensitivity analysis in the high-and low-risk groups,and the results suggested that Sorafenib and Paclitaxel were more effective in high-risk patients.Conclusion:The lncRNA model associated with copper death in hepatocellular carcinoma was constructed,and the prognostic value and immune infiltration of the model were explored.Compared with other clinical factors of hepatocellular carcinoma,the clinical and prognostic value of this risk model was higher than that of other clinical factors of hepatocellular carcinoma.The model not only possessed diagnostic value,but also was closely related to clinical stage,survival prognosis,immune infiltration,and drug sensitivity of hepatocellular carcinoma,and The five lncRNAs(AC026412.3,AC107021.2,AL355574.1,AL031985.3,AL117336.2),which constitute the model,also have certain diagnostic and clinical values and can be used as potential biomarkers of liver cancer with the possibility of becoming therapeutic targets.It provides a new perspective to further study the prognosis-related mechanisms in patients with hepatocellular carcinoma. |
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