恶性黑色素瘤泛素化相关基因预后风险模型的构建

Construction of a ubiquitination⁃related gene risk model for predicting survival in patients with malignant melanoma

目的:基于癌症基因图谱(TCGA)数据库构建预测恶性黑色素瘤患者预后的泛素化相关基因的风险模型,并对模型的预测效能进行验证。方法:从TCGA数据库和基因型-组织表达(GTEx)数据库中下载恶性黑色素瘤样本及正常组织的基因表达信息和临床数据。通过基因集合富集分析(GESA)、单因素及多因素Cox回归分析筛选出与预后相关的差异表达泛素化基因,并以此构建预测恶性黑色素瘤患者预后的风险模型。结果:筛选出9个显著差异表达的泛素化相关基因(KCTD7、KLHL2、NCCRP1、PSME1、RNF114、SKP2、SPSB1、SYVN1、UCHL3)用于模型构建。Kaplan-Meier分析结果提示高风险组的结局较低风险组更差(P<0.001),风险模型在预测1年、3年和5年总体生存率的ROC曲线下面积(AUC)值分别为0.775、0.743和0.785。多因素Cox回归分析表明风险评分是恶性黑色素瘤患者预后的独立预测因子(P<0.001)。结论:本研究发现由这9个泛素化相关基因构建的风险模型可以准确地预测恶性黑色素瘤患者的预后,这些基因有可能作为黑色素瘤新的生物标志物或治疗靶点。

Objective:To construct a ubiquitination-related gene risk model for predicting survival in patients with malignant melanoma based on the cancer genome atlas(TCGA)database,and to verify the predictive efficiency of the model.Methods:The gene expression profiles and clinical data of malig-nant melanoma patients were downloaded from the TCGA and the genotype-tissue expression(GTEx)database.The differentially expressed ubiquitin genes related to prognosis were screened by gene set enrichment analysis(GESA),univariate and multivariate Cox regression analysis,and a risk model was constructed to predict the prognosis of malignant melanoma patients.Results:We obtained nine ubiquitination-related genes(KCTD7,KLHL2,NCCRP1,PSME1,RNF114,SKP2,SPSB1,SYVN1,and UCHL3)to construct the risk model.Kaplan-Meier analysis showed the survival percentage of patients in the high-risk score group was lower than that in the low-risk score group(P<0.001).The area under the ROC curve(AUC)of the risk model for predicting overall survival of 1-,3-,and 5-year was 0.775,0.743,and 0.785,respectively.Univariate and multivariate Cox re-gression analysis showed that risk score was an independent predictor of prognosis in patients with malignant melanoma(P<0.001).Conclusion:This study shows the risk model constructed by those nine ubiquitination-related genes could accurately predict the prognosis of patients with malignant mel-anoma,and these genes have the potential to serve as new biomarkers or therapeutic targets for mela-noma.