早期肝移植物功能不良相关预测基因筛选及风险评分模型构建  

Establishment of a genomic model for predicting the likelihood of poor early graft function after liver transplantation

作　　者：余斌 夏天[1] 王彦峰[1] Yu Bin;Xia Tian;Wang Yanfeng(Zhongnan Hospital of Wuhan University,Institute of Hepatobiliary Diseases of Wuhan University,Transplant Center of Wuhan University,Hubei Key Laboratory of Medical Technology on Transplantation,Wuhan 430071,China)

机构地区：[1]武汉大学中南医院,武汉大学肝胆疾病研究院,武汉大学移植医学中心,移植医学技术湖北省重点实验室,武汉430071

出　　处：《中华器官移植杂志》2021年第6期359-364,共6页Chinese Journal of Organ Transplantation

摘　　要：目的筛选脑死亡供者(DBD)肝移植术后早期肝移植物功能不良(PEGF)相关分子标志物,并构建肝移植术后PEGF早期预测模型。方法基于美国基因表达数据库(GEO)GSE23649数据集中16例DBD供肝复灌2 h标本(8例发生PEGF,8例未发生PEGF)转录组数据,采用差异表达分析筛选PEGF相关基因;运用LASSO-Logistics回归筛选最佳建模基因集合构建风险评分模型,使用受试者工作特征曲线下面积(AUC)与Nomogram图评估模型预测效力及可视化;采用基因集富集分析(GSEA)探索PEGF相关生物学通路。结果本研究筛选出6个与DBD肝移植术后PEGF密切相关的关键基因,包括4个上调基因(HBB、PFDN5、RPS3A、RPS5)和2个下调基因(RPL22、FAM62B)。基于该6基因所构建的风险评分模型对DBD肝移植术后PEGF有良好的预测价值(AUC=1,P=0.0008)。GSEA提示DBD肝移植术后PEGF可能与"血管内皮生长因子"、"自然杀伤细胞介导的细胞毒性"等通路相关(均P<0.05)。结论该模型将有助于DBD肝移植术后早期精准评估PEGF风险,且未来有望联合常温机械灌注用于术前供肝质量评估。Objective To explore the poor early liver graft function(PEGF)-related biomarkers and establish a genomic model for PEGF prediction specific to liver transplantation(LT)with allografts of donation after brain death(DBD).Methods By data-mining a public GSE23649 dataset from the database of Gene Expression Omnibus(GEO),key PEGF-related genes in DBD liver biopsies after 2h reperfusion were identified by differential expression analysis.And LASSO-penalized Logistic regression model was utilized for selecting an optimal gene set.Receiver operating characteristic curves with its area under the curve(AUC)and a nomogram were generated for evaluating and visualizing its predictive capability for PEGF.Gene set enrichment analysis(GSEA)was performed for exploring the biological pathways underlying PEGF.Results Six key PEGF-related genes in DBD-LT were initially identified,including 4 up-regulated genes(HBB,PFDN5,RPS3A&RPS5)and 2 down-regulated genes(RPL22&FAM62B).A six-mRNA-based risk-scoring model was further established with an excellent predictive capability(AUC=1.000,P=0.0008).Four PEGF-related biological pathways in DBD livers,such as"VEGF"and"natural killer cell-mediated cytotoxicity",were identified by GSEA(all P<0.05).Conclusions The genomic model may effectively predict the likelihood of PEGF immediately after DBD-LT or even prior to transplantation in the context of normothermic machine perfusion.

关 键 词：肝移植 早期肝移植物功能不良 生物标志物 

分 类 号：R657.3[医药卫生—外科学]