Construction of hepatocellular carcinoma prognosis risk model and prediction of immunotherapy efficacy
Objective:To construct a prognostic risk model for hepatocellular carcinoma(HCC),and elucidate the immune characteristics and immunotherapy response in patients with different prognostic stratification.Methods:RNA-seq data of TCGA-LIHC and ICGC(LIRI-JP),and gene microarray data of GSE14520 and GSE54236 in hepatocellular carcinoma,as well as clinical informa-tion of the corresponding samples were downloaded.First,screening of differentially expressed genes in tumor and non-tumor tissue samples from TCGA-LIHC,GSE14520 and GSE54236.For the common differential genes,univariate cox regression analysis was per-formed using TCGA-LIHC data to obtain HCC prognosis-related genes.Five genes were randomly selected as a panel,and the optimal prognostic marker panel was screened among 10 000 panels using Lasso-cox regression analysis combined with a five-fold cross-valida-tion method.TCGA-LIHC data were used as training set to construct the prognostic risk model,and ICGC data were used as validation set to test the model performance.Tumor immune dysfunction and exclusion(TIDE)algorithm and Immunophenotypic score(IPS)were used to predict immunotherapy efficacy in patients in different prognostic groups.Results:Overall survival was significantly lon-ger in low-risk group of HCC patients compared with high-risk group.Tumor proliferation rate,Treg and Th2 cell chemotaxis,stromal remodeling,and pro-tumor cytokines were significantly increased in high-risk patients,while NK cells,Th1 cells,effector cells and endothelial cells were significantly increased in low-risk patients.Immune checkpoint analysis showed that PDCD1,CTLA4 and CD276 were up-regulated in high-risk patients,while PDCD1LG2 was upregulated in low-risk patients.TIDE score and IPS results predicted that patients in low-risk group had better efficacy to immunotherapy.Conclusion:This study constructed a prognostic risk model containing three genes,DNASE1L3,RDH16 and DLGAP5,which can effectively predict the prognosis of HCC patients and assist in clinical decision making for individualized immunotherapy.
国家科技期刊平台
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