基于外周血基因表达谱特征的肾移植排斥反应风险评估模型  

Risk evaluation model for kidney transplant rejection using peripheral blood gene expression profiling

作　　者：林杰胜 安会敏[1] 邵琨[1] 周全[1] 王祥慧[1] 周佩军[1] Lim Kiat Shenq;An Huimin;Shao Kun;Zhou Quan;Wang Xianghui;Zhou Peijun(Transplant Center,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院移植中心,200025

出　　处：《中华移植杂志（电子版）》2020年第5期273-278,共6页Chinese Journal of Transplantation(Electronic Edition)

摘　　要：目的以生物信息学方法,建立和验证基于肾移植受者外周血基因表达谱特征的排斥反应风险评估模型。方法对基因表达汇编公共数据库中与排斥反应相关的肾移植受者外周血基因表达谱,进行数据挖掘和整合分析,采用LIMMA差异表达分析法和LASSO回归法逐步进行特异基因的筛选。对筛选出的基因组合以Logistic回归分析法法建立肾移植排斥反应风险评估模型,并以受试者工作特征曲线分析、校准度分析和决策曲线分析对此模型进行验证和评价。P<0.05为差异有统计学意义。结果共筛选出15个对评估肾移植排斥反应风险有统计学意义的特异基因组合。利用此基因组合所建立的模型,可根据基因表达量计算,得出取值范围为0~100的排斥反应风险指数(RRS),当RRS截断值设定为35.55时,此模型的曲线下面积为0.836(0.812~0.859),准确度为76.3%,敏感度为73.0%,特异度为78.0%,阳性预测值为62.9%,阴性预测值为84.9%,并在决策曲线分析中表现出显著的临床获益优势。结论通过此模型计算得出的RRS,可无创性地量化评估受者发生移植肾排斥反应的风险,但仍需进一步的临床试验加以证实。Objective To develop and validate a risk evaluation model for kidney transplant rejection using bioinformatics methods.Methods This study conducted a data-mining and integrated analysis of blood-based gene expression profiling of kidney transplant recipients with rejection from the GEO database.Gene selection was performed progressively by LIMMA analysis and LASSO regression,followed by development of a risk evaluation model for kidney transplant rejection using the selected genes through Logistic regression.The utility of the proposed model was assessed by the ROC,calibration,and decision curve analyses.A P<0.05 was considered statistically significant.Results A 15-gene panel was selected according to its ability to evaluate the risk of rejection.The 15-gene panel was then used to establish a risk evaluation model and generate a risk of rejection score(RRS)by the gene expression values.RRS ranged from 0 to 100,when the cut-off of RSS was set to 35.55,the AUC,overall accuracy,sensitivity,specificity,and positive and negative predictive value of this model reached 0.836(0.812-0.859),76.3%,73.0%,78.0%,62.9%and 84.9%respectively.The decision curve analysis demonstrated significant advantage of clinical benefit using this model.Conclusions RRS generated by this model is capable of quantitatively evaluating the risk of rejection in a non-invasive manner.However,this model requires additional clinical trial study for further validation.

关 键 词：肾移植 生物信息学 移植物排斥反应 风险评估模型 外周血 基因表达谱 

分 类 号：R699.2[医药卫生—泌尿科学]