本研究通过筛选泛素化-铁死亡相关基因构建肝细胞癌(hepatocellular carcinoma,HCC)预后模型,并探究泛素化-铁死亡相关基因对HCC预后的影响.使用R包DESeq2对TCGA-LIHC数据集进行差异分析,获取HCC差异表达基因(HCC_DEGs).将 HCC_DEGs、泛素化相关基因(ubiquitination related genes,URGs)和铁死亡差异表达基因(ferroptosis_differentially expressed genes,FERR_EDGs)取交集获得泛素化和铁死亡相关基因(UBFE_EDGs),将UBFE_EDGs依次进行LASSO回归分析、单因素Cox回归分析和多因素Cox回归分析以筛选出最佳独立预后基因用于构建HCC预后模型(ubiquitination and fer-roptosis-related prognostic model,UBFE).由生存曲线、ROC曲线和校正曲线评估UBFE的预测准确性.单因素Cox回归分析、多因素Cox回归分析评估UBFE风险评分是否为HCC的预后独立危险因素,并构建列线图模型.ssGSEA分析和单细胞测序数据分析用于评估UBFE与泛素化及铁死亡的相关性.结果显示,HCC_DEGs、URGs和FERR_EDGs取交集得到45个UBFE_EDGs,依次进行LASSO回归分析、单因素Cox回归分析和多因素Cox回归分析筛选出2个UBFE_EDGs(DCAF13和UBE2C)用于构建HCC预后模型UBFE.生存曲线、ROC曲线和校准曲线分析显示UBFE高风险评分组(HighUBFE)与HCC患者预后差显著相关,UBFE具有较好的预测准确性.单因素Cox回归分析和多因素Cox回归分析结果显示UBFE风险评分是HCC患者预后的独立危险因素,UBFE联合TNM分期的预测准确性更高,列线图预测HCC患者的1年、2年和3年生存率与实际生存率的一致性较高.ssGSEA分析和单细胞分析的结果均显示UBFE风险评分与泛素化呈正相关性,与铁死亡呈负相关性,UBFE高风险评分组的铁死亡拮抗反应高于UBFE低风险评分组的.本研究构建的UBFE在预测HCC患者的预后方面具有较好的表现,DCAF13和UBE2C可能通过泛素化和铁死亡通路影响肝细胞癌的进展及患者预后.
A Novel Ubiquitination and Ferroptosis-related Gene Signature for Prognosis A-nalysis of Hepatocellular Carcinoma
This study constructed a prognostic model for hepatocellular carcinoma(HCC)by screening genes related to ubiquitination and ferroptosis,and explored the impact of ubiquitination and ferroptosis-related genes on the prognosis of HCC.The DESeq2 package was used for differential analysis of the TCGA-LIHC dataset to obtain HCC differentially expressed genes(HCC_DEGs).The ubiquiti-nation and ferroptosis differentially expressed genes(UBFE_EDGs)obtained from the intersection of HCC_DEGs,ubiquitination relat-ed genes(URGs),and ferroptosis differentially expressed genes(FERR_EDGs)were sequentially applied to LASSO regression analy-sis,univariate Cox regression analysis and multivariate Cox regression analysis to identify the optimal independent prognostic genes for constructing the ubiquitination and ferroptosis-related prognostic model(UBFE).Survival curves,ROC curves,and calibration curves were used to evaluate the predictive accuracy of UBFE.Univariate Cox regression analysis and multivariate Cox regression analysis were performed to assess whether the UBFE risk score is an independent prognostic factor for HCC,and a nomogram was constructed.ssGSEA analysis and single-cell RNA sequencing data analysis were used to explore the correlations of UBFE with ubiquitination and ferroptosis.The results show that 45 UBFE_EDGs were obtained from the intersection of HCC_DEGs,URGs,and FERR_EDGs.LAS-SO regression analysis,univariate Cox regression analysis,and multivariate Cox regression analysis were performed sequentially,and two UBFE_EDGs(DCAF13 and UBE2C)were identified for constructing the UBFE.Survival curves,ROC curves,and calibration curves analysis showed a significant correlation between the UBFE high-risk score group(HighUBFE)and poor prognosis in HCC pa-tients,indicating good predictive accuracy of UBFE.The results of univariate Cox regression analysis and multivariate Cox regression a-nalysis demonstrated that the UBFE risk score was an independent risk factor for HCC prognostic.The prediction accuracy of UBFE combined with TNM staging was higher,and the consistency between the predicted 1-year,2-year,and 3-year survival rates of HCC patients and the actual survival rate was high in nomogram.Both ssGSEA analysis and single-cell RNA sequencing data analysis re-vealed a positive correlation between the UBFE risk score and ubiquitination,as well as a negative correlation with ferroptosis.The UBFE high-risk score group exhibited a stronger inhibitory effect on ferroptosis compared to the UBFE low-risk score group.The UBFE constructed in this study has shown good performance in predicting the prognosis of HCC patients.DCAF13 and UBE2C may affect the progression of hepatocellular carcinoma and patient prognosis through ubiquitination and ferroptosis pathways.
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