TTN突变相关基因特征对肝细胞肝癌预后的预测价值  

Predictive value of TTN mutation-related gene characteristics on prognosis of hepatocellular carcinoma

作　　者：毕艳青 黄容 宋伟[2] 张子英 田梓璇 刘敏 包含 闫涛 夏远 张楠 张星光 BI Yanqing;HUANG Rong;SONG Wei;ZHANG Ziying;TIAN Zixuan;LIU Min;BAO Han;YAN Tao;XIA Yuan;ZHANG Nan;ZHANG Xingguang(Department of Biostatistics,Public Health College,Inner Mongolia Medical University,Inner Mongolia Hohhot 010110,China;Department of Biochemistry and Molecular Biology,State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and School of Basic Medicine,Peking Union Medical College,Beijing 100005,China;Department of Biostatistics,Basic Medical College,Inner Mongolia Medical University,Inner Mongolia Hohhot 010110,China)

机构地区：[1]内蒙古医科大学公共卫生学院生物统计学系,内蒙古呼和浩特010110 [2]北京协和医学院基础医学研究所,基础医学科学院医学分子生物学国家重点实验室生物化学与分子生物学系,北京100005 [3]内蒙古医科大学基础医学院生物统计学系,内蒙古呼和浩特010110

出　　处：《现代肿瘤医学》2023年第12期2275-2283,共9页Journal of Modern Oncology

基　　金：国家自然科学基金项目(编号:82160639);内蒙古医科大学面上项目(编号:YKD2021MS001)。

摘　　要：目的:寻找新的有效生物标志物用于肝细胞肝癌(hepatocellular carcinoma,HCC)的早期诊断和预后预测。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)下载HCC样本的转录组和临床数据,利用TCGA队列的mRNA丰度数据和TTN突变信息,根据野生型TTN和突变型TTN HCC患者之间的基因表达差异,表征特定的TTN突变相关特征。生存分析筛选与HCC患者预后相关的基因,单因素Cox回归构建预后风险模型。通过GO注释、途径富集分析、京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)和基因集富集分析(gene set enrichment analysis,GSEA)确定与HCC患者预后相关的差异表达基因(differentially expressed genes,DEGs)的功能。结果:通过单变量Cox回归和Kaplan-Meier生存分析确定的5个基因,腹前同源盒1(ventral anterior homeobox 1,VAX1)、基质金属蛋白酶3(matrix metalloproteinase 3,MMP3)、CXC型趋化因子5(CXC-type chemokine 5,CXCL5)、转酮醇酶样蛋白1(transketolase-like protein 1,TKTL1)和电压门控钾通道Kv1.3(voltage-gated potassium channel Kv1.3,KCNA3)构成了HCC患者总生存(overall survival,OS)预后基因特征。结论:5个TTN突变相关基因,包括VAX1、MMP3、CXCL5、TKTL1和KCNA3,可作为HCC患者生存和预后的潜在生物标志物和治疗靶点。Objective:To find new effective biomarkers for early diagnosis and prognosis prediction of hepatocellular carcinoma(HCC).Methods:The transcriptomic and clinical data of HCC samples were downloaded from The Cancer Genome Atlas(TCGA).The mRNA abundance data and TTN mutation information from TCGA cohort were utilized to characterize a specific TTN mutation-associated signature according to gene expression differences between wild-type TTN and mutated TTN HCC patients.The genes related to the prognosis of HCC patients were screened by survival analysis,and the prognostic risk model was constructed by univariate Cox regression.After that,GO annotation,pathway enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)and gene set enrichment analysis(GSEA)were used to determine that the function of differentially expressed genes(DEGs)related to the prognosis of HCC patients.Results:Five genes,VAX1(ventral anterior homeobox 1),MMP3(matrix metalloproteinase 3),CXCL5(CXC-type chemokine 5),TKTL1(transketolase-like protein 1)and KCNA3(voltage-gated potassium channel Kv1.3)determined by univariate Cox regression and Kaplan-Meier survival analysis constituted the overall survival(OS)prognostic gene characteristics of patients with HCC.Conclusion:Five TTN mutation-related genes,including VAX1,MMP3,CXCL5,TKTL1,and KCNA3,can be used as potential biomarkers and therapeutic targets for the survival and prognosis of HCC patients.

关 键 词：TTN突变 基因标记 预后 功能分析 肝细胞肝癌 

分 类 号：R735.7[医药卫生—肿瘤]