乳酸代谢相关基因预测肝细胞癌预后的风险评分模型的构建  

The Construction of Risk Scoring Model for Predicting the Prognosis of Hepatocellular Carcinoma Based on Lactate Metabolism Related Genes

作　　者：汪玲 张青[1] 刘军 姜钰环 李慧明 WANG Ling;ZHANG Qing;LIU Jun;JIANG Yuhuan;LI Huiming(Department of Nuclear Medicine,The First AffiliatedHospital of Nanchang University,Nanchang 330006,China;Department of Clinical Laboratory,The First AffiliatedHospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]南昌大学第一附属医院核医学科,江西南昌330006 [2]南昌大学第一附属医院检验科,江西南昌330006

出　　处：《标记免疫分析与临床》2023年第9期1555-1559,共5页Labeled Immunoassays and Clinical Medicine

基　　金：江西省教育厅科技重点项目(编号:GJJ210135);江西省中医药管理局科技计划项目(编号:2022B921,2022B966);江西省卫健委科技计划项目(编号:202130329)。

摘　　要：目的鉴定肝细胞癌相关乳酸代谢基因,并基于相关基因构建风险评分模型预测肝细胞癌预后。方法使用TCGA数据库收集了377例肝细胞癌患者的临床信息和转录组数据,通过Cox单因素分析、Lasso回归筛选乳酸代谢相关基因,构建肝细胞癌患者预后多因素风险评分模型,采用TCGA内部验证数据集验证一致性。结果在获取的303个乳酸代谢相关基因中,从肿瘤组和正常组中筛选了91个差异表达大于2倍的基因;训练组中通过Cox单因素分析、Lasso回归筛选出3个差异表达基因ACTN3、DTYMK和HTRA2,3个基因的高表达均与HCC患者不良预后相关,基于3个代谢基因的表达构建肝细胞癌患者预后预测模型对各肿瘤样本评分,其中年龄、分期和风险评分均为HCC患者OS的独立预测因素,TCGA内部验证数据集(n=192)验证不同风险评分对患者生存的影响,结果与训练集一致。进一步分析发现高风险评分组患者的IFN反应力更低。结论基于乳酸代谢相关基因构建的风险评分模型可较好地预测HCC患者预后,乳酸代谢基因的研究有助于深入理解HCC发生发展的分子机制,为HCC患者治疗提供新的潜在靶点。Objective To identify lactate metabolism genes and construct a risk scoring model based on these genes to predict the prognosis in hepatocellular carcinoma.Methods The clinical information and transcriptome data of 377 patients with hepatocellular carcinoma were collected from TCGA database.Genes related to lactate metabolism were screened through Cox single factor analysis and lasso regression,and a multivariate risk score model for prognosis of hepatocellular carcinoma patients was constructed.The consistency was verified using TCGA internal validation data set.Results Among 303 genes related to lactate metabolism obtained,91 genes with differential expression greater than 2 times were selected from the tumor group and the normal group;In the training group,three differentially expressed genes:ACTN3,DTYMK,and HTRA2 were selected through Cox univariate analysis and lasso regression.The high expressions of these three genes were associated with a poor prognosis in HCC patients.Based on expressions of these three metabolic genes,a prognostic prediction model for hepatocellular carcinoma patients was constructed to score each tumor sample.Age,stage,and risk score were independent predictors of OS in HCC patients,The TCGA internal validation dataset(n=185)was used to validate the impact of different risk scores on patient survival,and the results were consistent with the training set.Further analysis revealed that patients in the high-risk scoring group had a lower IFN reactivity.Conclusion A risk scoring model based on lactate metabolism related genes can effectively predict the prognosis of HCC patients.The study of lactate metabolism genes helps to deeply understand the molecular mechanisms of HCC occurrence and development,providing novel potential targets for the treatment of HCC patients.

关 键 词：肝细胞癌 乳酸代谢 预后模型 基因 

分 类 号：R735.7[医药卫生—肿瘤]