AML铜死亡相关lncRNA预后风险模型的构建

CONSTRUCTION OF A PROGNOSTIC RISK MODEL BASED ON CUPROPTOSIS-RELATED LNCRNAS FOR ACUTE MYELOID LEUKEMIA

目的采用生物信息学分析方法对癌症基因组图谱(TCGA)数据库中急性髓细胞白血病(AML)数据进行分析,建立铜死亡相关长链非编码RNA(lncRNA)预后风险模型,并进行效能验证。方法通过共表达和单因素Cox回归分析鉴定与预后相关的铜死亡相关lncRNA。采用lasso回归和多因素Cox回归分析选出最优的铜死亡相关lncRNA构建预后风险模型,根据风险模型评分将AML病人分为高、低风险组。采用校准曲线、C指数、受试者工作特征(ROC)曲线以及临床决策曲线评价预测模型。结果共获得4个与AML病人预后相关性最佳的铜死亡相关lncRNA(LINC01547、LINC02356、NORAD和AC000120.1),基于此4个lncRNA构建列线图模型来预测AML病人1、3、5年预后,预测的准确性较高,C指数为0.686,在训练集中1、3、5年预后预测的ROC曲线下面积分别为0.758、0.717和0.804,在测试集中则分别为0.704、0.682和0.927。在训练集和测试集中,高风险组病人的生存率均明显低于低风险组。结论基于铜死亡相关lncRNA构建的预后风险模型评分是一个独立的预后因素,可有效预测AML病人的预后。

Objective To establish and validate a prognostic risk model based on cuproptosis-related long non-coding RNAs(lncRNAs)for acute myeloid leukemia(AML)using AML data in The Cancer Genome Atlas database through bioinforma-tic analysis.Methods Cuproptosis-related lncRNAs associated with AML prognosis were determined by co-expression and univariable Cox regression analyses.Lasso regression and multivariable Cox regression analyses were performed to identify the optimal cuproptosis-related lncRNAs for constructing the prognostic risk model.Patients with AML were divided into high-and low-risk groups according to the risk model.The prediction model was evaluated by using the calibration curve,C index,receiver operating characteristic(ROC)curve,and decision curve.Results Four optimal cuproptosis-related lncRNAs(LINC01547,LINC02356,NORAD,AC000120.1)associated with the prognosis of patients with AML were obtained.The nomogram model based on the four lncRNAs showed high accuracy when predicting the 1,3,and 5 year outcomes of patients with AML patients.The C index was 0.686.The areas under the ROC curves for 1,3,and 5 year outcome prediction in the training set were 0.758,0.717,and 0.804,respectively;and those in the test set were 0.704,0.682,and 0.927,respectively.In both the training and test sets,the survival rate of the high-risk group was significantly lower than that of the low-risk group.Conclusion The risk model score based on cuproptosis-related lncRNAs was an independent prognostic factor,which could effectively predict the prognosis of patients with AML.