线粒体翻译起始因子(MTIF2)基因甲基化的特征及其与肝细胞癌发生的相关性分析  

Characteristics of mitochondrial translational initiation factor 2 gene methylation and its association with the development of hepatocellular carcinoma

作　　者：谢华杰 常凯 王艳艳 那琬琳 蔡欢 刘霞 江忠勇 胡宗海 刘媛 XIE Huajie;CHANG Kai;WANG Yanyan;NA Wanlin;CAI Huan;LIU Xia;JIANG Zhongyong;HU Zonghai;LIU Yuan(Department of Clinical Laboratory,The General Hospital of Western Theater Command,Chengdu 610083,China;Department of Clinical Laboratory,Affiliated Cancer Hospital of Chengdu Medical College,Chengdu Seventh People’s Hospital,Chengdu 610041,China)

机构地区：[1]中国人民解放军西部战区总医院检验科,成都610083 [2]成都市第七人民医院(成都医学院附属肿瘤医院)检验科,成都610041

出　　处：《临床肝胆病杂志》2025年第2期284-291,共8页Journal of Clinical Hepatology

基　　金：四川省自然科学基金(2022NSFSC1415);西部战区总医院应用基础研究项目(2021-XZYG-C22)。

摘　　要：目的结合生物信息学分析方法对线粒体翻译起始因子(MTIF2)基因的甲基化特征进行分析,并探讨其与肝细胞癌发生发展的关系。方法应用MethSurv、EWAS Data Hub软件对MTIF2甲基化样本进行标准化分析和聚类分析,内容包括生存曲线分析、甲基化特征分析、肿瘤信号通路相关性及泛癌数据库比对分析。计量资料两组间比较采用成组t检验;多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。使用Cox比例风险模型基于患者CpG部位的甲基化水平执行单变量和多变量生存分析。通过Kaplan-Meier图标识较低和较高甲基化患者组之间的生存差异。Log-likelihood ratio法用于组间生存差异分析。结果MTIF2甲基化整体聚类表明在种族、人种、BMI、年龄等特征间MTIF2基因甲基化水平没有明显差异。Kaplan-Meier生存曲线分析发现,MTIF2基因N-Shore高甲基化的患者预后明显好于低甲基化患者(HR=0.492,P<0.001),而CpG island和S-Shore甲基化的高低与生存率无明显差异(P值均>0.05)。基于不同年龄、性别、BMI、人种、种族、临床分期绘制MTIF2基因甲基化谱发现,随年龄增长会降低MTIF2基因N-Shore和CpG island的甲基化水平,白种人的MTIF2基因N-Shore的甲基化水平明显低于亚洲人(P<0.05),临床分期Ⅳ期患者MTIF2基因N-Shore和CpG island的甲基化水平明显低于Ⅰ/Ⅱ期患者(P值均<0.05)。临床验证试验表明,Ⅲ/Ⅳ期肝细胞癌患者MTIF2甲基化水平明显低于Ⅰ/Ⅱ期患者(P<0.05),且低于健康人群(P<0.05)。结论MTIF2基因N-Shore低甲基化是肝细胞癌发生发展的危险因素。Objective To investigate the characteristics of mitochondrial translational initiation factor 2(MTIF2)gene methylation and its association with the development and progression of hepatocellular carcinoma(HCC).Methods MethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples,including survival curve analysis,methylation signature analysis,the association of tumor signaling pathways,and a comparative analysis based on pan-cancer database.The independent-samples t test was used for comparison between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site.The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level,and the Log-likelihood ratio method was used for survival difference analysis.Results Global clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races,ethnicities,BMI levels,and ages.The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation(hazard ratio[HR]=0.492,P<0.001),while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels(P>0.05).The methylation profile of the MTIF2 gene based on different ages,sexes,BMI levels,races,ethnicities,and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age,and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population(P<0.05);the

关 键 词：线粒体翻译起始因子 甲基化 癌 肝细胞 计算生物学 

分 类 号：R73[医药卫生—肿瘤]