Identification of prognostic genes and construction of prognostic model of hepatocellular carcinoma based on DNA damage response
Objective To screen differential expressed-DNA damage response associated genes(DEDDR)and construct a prognostic model for hepatocellular carcinoma(HCC).Methods The"limma"R package was employed to identify differentially expressed genes(DEGs)between HCC samples and normal samples from the TCGA-LIHC dataset,and the DEGs were taken to intersect with 276 DDR genes to obtain DEDDR.Univariate Cox analysis and Lasso regression analysis were performed to establish the DEDDR prognostic mod-el.The accuracy of the model was evaluated using ROC curves.Univariate and multivariate Cox regression an-alyses were conducted to determine whether the DEDDR prognostic model risk score was an independent prog-nostic factor for HCC.External validation was carried out using the LIHC data provided by the International Cancer Genome Consortium(ICGC).Lastly,GSEA and immune infiltration analysis were conducted on the low-DEDDR and high-DEDDR groups.Results The intersection of 1 361 DEGs with 276 DDR genes resulted in 25 DEDDR genes.LASSO regression analysis identified 4 DEDDR(TTK,NSMCE2,NUDT1,NEIL3)for constructing the prognostic model.Patients in the low-DEDDR group exhibited higher survival rates compared to the high-DEDDR group.ROC curves indicated that the model predicted that 1-year,2-year,and 3-year sur-vival rates for HCC patients had the AUC values of 0.77,0.70,and 0.68,respectively.Univariate and multi-variate Cox regression analyses demonstrated that the DEDDR prognostic model risk score was an independent prognostic factor for HCC patients with higher AUC values than other clinical pathological features.Further validation using LIHC data of ICGC confirmed the model's accuracy and clinical applicability.GSEA analysis revealed that the high-DEDDR group was mainly enriched in pathways related to cell cycle,cellular senescence,and DNA replication.Additionally,the abundance of type 2 helper T cells(Th2)was higher in the high-DED-DR group,while the abundance of eosinophils was lower.Conclusion The DEDDR prognostic model has showed good performance in predicting the prognosis of HCC patients,and can serve as a reference for prog-nostic evaluation and identification of high-risk individuals.
万方数据
维普
