文章摘要
时国东,陈 群,胡青桥,卢 诚,袁 昊,孟令东,黄徐敏,陆怡超,沈 鹏,张奕晗,张 凯,张静静,苗 毅,蒋奎荣.基于TCGA数据库挖掘胰腺癌预后相关甲基化位点[J].南京医科大学学报,2020,(8):1135~1139
基于TCGA数据库挖掘胰腺癌预后相关甲基化位点
Identification of DNA methylation sites related to the prognosis of pancreatic ductal adenocarcinoma based on the TCGA datebase
投稿时间:2019-11-19  
DOI:10.7655/NYDXBNS20200810
中文关键词: 胰腺导管腺癌  TCGA  甲基化  mRNA  预后
英文关键词: pancreatic ductal adrenocarcinoma  TCGA  methylation  mRNA  prognosis
基金项目:国家自然科学基金(81902455,81871980);江苏省医学重点人才项目(ZDRCB2016004);江苏省医学重点学科?普通外科学(ZDXKA2016005)
作者单位
时国东 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
陈 群 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
胡青桥 南京医科大学第一附属医院核医学科江苏 南京 210029 
卢 诚 南京同仁医院普外科江苏 南京 211102 
袁 昊 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
孟令东 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
黄徐敏 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
陆怡超 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
沈 鹏 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
张奕晗 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
张 凯 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
张静静 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
苗 毅 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
蒋奎荣 南京医科大学第一附属医院胰胆中心江苏 南京 210029 
摘要点击次数: 201
全文下载次数: 139
中文摘要:
      目的:通过对肿瘤基因组图谱(The Cancer Genome Atlas,TCGA)数据库内胰腺导管腺癌(pancreatic ductal adrenocarcinoma,PDAC)相关数据的研究,从全基因组水平发现影响PDAC预后的甲基化位点及基因。方法:从TCGA网站下载2016年1月28日更新版本的有关PDAC的临床数据、甲基化数据(基于Illumina Methylation 450芯片)及转录组数据(基于Illumina Hiseq测序)。纳入兼具预后数据和甲基化数据的患者179例,应用Cox比例风险模型分析每个位点甲基化水平与PDAC患者总体生存率的关系。进一步纳入兼有甲基化数据及转录组数据的患者173例,分析甲基化水平与对应mRNA表达水平的关系。最后分析mRNA表达水平与PDAC患者总体生存率的关系。结果:用于甲基化预后分析的179例患者年龄为(64.64±10.96)岁,用于相关性分析和mRNA预后分析的173例患者年龄为(64.46±10.91)岁,两者中位生存时间均为20.1个月。本研究发现的与PDAC预后关系最显著的前20个甲基化位点中,11个位点的高甲基化水平为PDAC预后的危险因素,9个为保护因素。位于ZNF438基因5′UTR区的cg01656216探针靶向的位点与PDAC预后相关最显著(HR=0.37,95%CI:0.24~0.56,P=4.11×10-6)。进一步发现8个位点甲基化水平与相应mRNA表达水平呈负相关(r<-0.3,P < 0.05),其中PKP3(cg20268054)和EFNB2(cg22179913)的mRNA表达水平还与预后有关(HR=1.66,95%CI:1.06~2.61,P=0.027;HR=1.86,95%CI:1.21~2.88,P=0.005)。结论:通过对TCGA数据库PDAC样本的分析发现,PKP3和EFNB2基因的甲基化水平与PDAC预后相关,可进一步发掘其作为PDAC预后相关生物标志物的潜能。
英文摘要:
      Objective:To investigate the DNA methylation sites related to the prognosis of patients with pancreatic ductal adenocarcinoma(PDAC)at the whole?genome level by utilizing The Cancer Genome Atlas(TCGA)database. Methods:The clinical data,DNA methylation data detected on Illumina Humanmethylation450k beadchip and transcriptome data produced by Illumina Hiseq of PDAC patients were downloaded from TCGA database(version 2016_01_28). We finally chose 179 cases containing both of clinical data and methylation expression profiles to analyze the effect of methylation level on survival by Cox’s proportional hazards model. Five factors including age,sex,location,histological grade and pathological stage were used to correct hazard ratio and P value. Next we chose 173 cases containing both of gene expression and methylation expression profiles to explore correlation between methylation level and mRNA expression level. Furthermore,we also evaluated the expression level of mRNAs with the prognosis. Results:The age of 179 patients was 64.64±10.96 years and that of 173 patients was 64.46 ± 10.91 years. The median survival times were both 20.1 months. Among the top 20 methylation sites,hypermethylation of 11 sites and hypomethylation of other 9 sites were associated with worse prognosis. The strongest site influencing the survival for PDAC in this study was cg01656216,which was located in the 5′UTR region of ZNF438(P=4.11×10-6,HR=0.37,95%CI:0.24?0.56). The methylation levels of 8 sites showed significant inverse correlation with mRNA expression levels(r<-0.3,P < 0.05). In addition,the mRNA expression level of PKP3(cg20268054)and EFNB2(cg22179913)were also related to the survival of PDAC(HR=1.66,95%CI:1.06?2.61,P=0.027;HR=1.86,95%CI:1.21?2.88,P=0.005). Conclusion:Based on the analysis of TCGA database,methylation sites in PKP3 and EFNB2 genes regions are significantly associated with PDAC prognosis,whose potential for predicting prognosis of PDAC can be further studied.
查看全文   查看/发表评论  下载PDF阅读器