Construct a model to predict the prognosis of patients with hepatocellular carcinoma based on cuprotosis-related ferroptosis genes
Objective It is to construct a prognostic model based on cuprotosis-related ferroptosis genes,and evaluate their predictive ability in patients with hepatocellular carcinoma,and explore their relationship with immune function and tumor mutation burden.Methods The Cancer Genome Atlas database(TCGA)was used to analyze the ferroptosis genes and survival data related to cuprotosis in 370 cases of patients with hepatocellular carcinoma,and the dataset was randomly divided into a training group and a testing group.The ferroptosis genes related to cuprotosis were screened for risk model construction by using Lasso regression and Cox model construction.The independence of the risk model on the prognosis of hepatocellular carcinoma was verified by univariate and multivariate Cox regression analysis,and the relationships between the risk model and immune function and tumor mutation burden were analyzed.Results Three cuprotosis-related ferroptosis genes EIF2S1,G6PD and NRAS were selected in the multivariate Cox regression data.EIF2S1,G6PD and NRAS were in-dependently correlated with survival in the training group(all P＜0.05),they were used to establish the risk model.Kap-lan Meier analysis showed that compared with the low-risk group,the patients of the high-risk group had a shorter survival period and lower survival rate(both P＜0.05).Univariate Cox regression analysis showed that HR of the risk model con-structed with cuprotosis-related ferroptosis genes was 1.734 with 95%CI 1.494-2.034(P＜0.001).Multivariate Cox re-gression analysis showed that HR of the risk model constructed with cuprotosis-related ferroptosis genes was 1.661 with 95%CI 1.397-1.976(P＜0.001).ROC curve analysis showed that the area under the curve(AUC)of the risk model predicting survival at years 1,3,and 5 for patients with hepatocellular carcinoma was 0.760,0.663,and 0.636,respec-tively.The Kaplan Meier survival curve analysis with this risk model showed that compared with early patients with hepatocel-lular carcinoma,the patients with late hepatocellular carcinoma had a shorter survival period and lower survival rate(P＜0.05).There were statistically significant differences in the expressions of TypeⅡIFN Response,ParaInflammation,APC co-stimulation,CCR,Check point and MHC classⅠbetween the high-risk group and low-risk group(all P＞0.05).The survival period of patients with hepatocellular carcinoma in the high tumor mutation burden group was significantly lower than that in the low tumor mutation burden group(P＜0.05).Conclusion The risk model based on cuprotosis-related fer-roptosis genes can effectively distinguish the prognosis of patients with hepatocellular carcinoma,it is closely related to im-mune function and tumor mutation burden.
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