中文摘要：

目的 ：通过对TCGA（The Cancer Genome Atlas）数据库的数据挖掘,扫描全基因组范围内的肺腺癌预后相关的甲基化位点。方法：采用2016年4月从TCGA网站下载的肺腺癌预后数据及基于Illumina Methylation 450芯片的全基因组甲基化数据,经过数据连接,纳入同时有临床预后信息和甲基化数据的肺腺癌患者232例。采用Cox比例风险模型分析各位点甲基化水平对肺腺癌总生存率的影响,并评估其与对应基因m RNA表达的相关性,进一步评估m RNA表达对肺腺癌预后的影响。结果：纳入的232例肺腺癌患者的平均年龄为（64.823±9.300）岁,平均生存时间为（20.217±17.067）个月。本研究发现肺腺癌预后相关最显著的甲基化位点为位于基因EHBP1区域的cg03955927（P=1.98×10-7）,对应的HR值及95%可信区间为0.605（0.501-0.731）。筛选的肺腺癌预后关联性最强的前20个甲基化位点中,17个位点的高甲基化水平为肺腺癌预后的保护因素,其他3个为危险因素。5个甲基化位点的甲基化水平与对应基因的m RNA表达相关,其中cg12013757对应的KRI1基因的m RNA表达与肺腺癌的预后有关（HR：1.316,95%CI：1.109-1.561,P=0.001 6）。结论 ：本研究通过对TCGA数据库的挖掘,初步发现KRI1基因的甲基化位点的甲基化水平对肺腺癌的预后有影响,可以作为为肺癌预后的生物标志物进一步研究。

英文摘要：

Objective：The aim of this study was to investigate the DNA methylation sites associated with the prognosis of patients with lung adenocarcinoma in the whole genome-level with the data-mining for TCGA （The Cancer Genome Atlas）public database. Methods：The clinical data of lung adenocarcinoma patients was downloaded from TCGA database in April,2016,as well as genome-wide DNA methylation data with Illumina’s Infinum Human Methylation 450 Bead Chips （HM450）. After data linked,232 cases of lung adenocarcinoma with the information of both clinic and methylation were finally included in this study. A Cox’s proportional hazards regression analysis was conducted to assess the relationship between DNA methylation levels or mRNA expression and the overall survival of lung adenocarcinoma patients,further evaluate the correlation between DNA methylation and mRNA expression,as well as the relationship between mRNA expression and lung adenocarcinoma survival. Results：The mean age and survival time of 232 people with lung adenocarcinoma was （64.823 ± 9.300）years and （20.217 ± 17.067）months. cg03955927 located in EHBP1 was found to be the strongest methylation site in this study which was associated with the survival of lung adenocarcinoma,adjusted HRs（hazard ratio）were 0.605 （0.501-0.731）,P=1.98×10-7. Among the strongest 20 methylation sites,the high methylation level of 17 sites were considered as protective factors for the survival of lung adenocarcinoma and that of other 3 sites were risk factors. The methylation levels of 5 methylation sites affect the targeted gene’s mRNA expression. In addtion,the mRNA expression of KRI1 was associated with the survival of lung adenocarcinoma,adjusted HRs were 1.316（1.109-1.561）with a P value of 0.001 6. Conclusion：With TCGA data mining,we found that methylation site in KRI1 gene region is highly related to lung adenocarcinoma prognosis,as further study biomarker related to prognosis of lung cancer.