临床与病理杂志2024,Vol.44Issue(10):1331-1342,12.DOI:10.11817/j.issn.2095-6959.2024.240600
基于铜死亡和铁死亡相关lncRNA的肝细胞癌预后模型的构建及评估
Construction and evaluation of a prognostic model for hepatocellular carcinoma based on cuproptosis-and ferroptosis-related lncRNAs
摘要
Abstract
Objective:Cuproptosis and ferroptosis can regulate the biological behavior of tumors.Therefore,biomarkers associated with cuproptosis,ferroptosis,and long non-coding RNA(lncRNA)are expected to become candidate biomarkers for clinical cancer therapy.This study aims to screen cuproptosis-and ferroptosis-related lncRNAs from The Cancer Genome Atlas(TCGA)database and construct a prognostic risk model for hepatocellular carcinoma(HCC). Methods:This study utilized various bioinformatics methods,including Pearson correlation analysis,differential analysis univariate Cox regression analysis,least absolute shrinkage and selection operator(LASSO)analysis,and multivariate Cox regression analysis to construct a predictive model and divide patients into high-risk and low-risk groups.Kaplan-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curve analysis were performed to assess the clinical efficacy of the model.Additionally,functional enrichment analysis,gene mutation analysis,immune-related analysis,and drug sensitivity analysis were performed based on the high-and low-risk groups defined by the model. Results:A total of 2 074 cuproptosis-and ferroptosis-related differential lncRNAs most closely associated with the prognosis of HCC were integrated into 10 related lncRNA(LINC02561,AC006372.2,AL603839.2,AC009974.2,POLH-AS1,AP006222.2,AP001631.2,AC073573.1,AC244034.2,and AC007998.3)to construct the risk model.The K-M survival curve showed significant survival differences between the different risk groups(P<0.001).ROC curve analysis indicated that the area under curve(AUC)for the training set was 0.805,and the AUC for the test set was 0.742.Patients in the high-risk group had a higher frequency of gene mutations,worse prognosis,and were more likely to benefit from immune checkpoint inhibitors(ICIs)therapy.In the high-risk group,most chemotherapy drugs(e.g.,doxorubicin,paclitaxel,sunitinib)showed lower half-maximal inhibitory concentrations. Conclusion:The risk model based on cuproptosis-and ferroptosis-related lncRNA expression can independently predict the survival of HCC patients and may provide references for patient treatment with immune therapy and chemotherapy.关键词
铜死亡/铁死亡/长链非编码RNA/肝细胞癌/预后Key words
cuproptosis/ferroptosis/long non-coding RNA/hepatocellular carcinoma/prognosis引用本文复制引用
龚晓文,庞成帅,董辰阳,宣月蓉,曹锐,梁超杰..基于铜死亡和铁死亡相关lncRNA的肝细胞癌预后模型的构建及评估[J].临床与病理杂志,2024,44(10):1331-1342,12.基金项目
山西省应用基础研究计划项目(201901D211480).This work was supported by the Applied Basic Research Program of Shanxi Province,China(201901D211480). (201901D211480)