基于TCGA数据库挖掘肺腺癌预后相关的甲基化位点和基因

发布时间：2018-06-01 23:08

本文选题：肺腺癌 + TCGA　；参考：《南京医科大学学报(自然科学版)》2016年06期

【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。
[Abstract]:Aim: to scan the genome-wide prognostic methylation sites of lung adenocarcinoma by mining data from TCGA(The Cancer Genome Atlas) database. Methods: the prognosis data of lung adenocarcinoma and the whole genome methylation data based on Illumina Methylation 450 chip were downloaded from TCGA website in April 2016. The data were connected to the data and included in 232 patients with lung adenocarcinoma with clinical prognosis information and methylation data. Cox proportional risk model was used to analyze the effect of point methylation level on the overall survival rate of lung adenocarcinoma, and to evaluate the correlation between the expression of m RNA and the expression of corresponding gene m RNA, and to further evaluate the influence of m RNA expression on the prognosis of lung adenocarcinoma. Results: the mean age of 232 patients with lung adenocarcinoma was 64.823 卤9.300 years old and the mean survival time was 20.217 卤17.067 months. In this study, we found that the most significant methylation site associated with prognosis of lung adenocarcinoma was cg03955927(P=1.98 脳 10-7 located in the region of gene EHBP1, and the corresponding HR value and 95% confidence interval were 0.605 / 0.501 / 0.731g. The hypermethylation level of 17 of the top 20 methylation sites in the selected lung adenocarcinoma was the protective factor for the prognosis of lung adenocarcinoma. The other three were risk factors. The methylation level of 5 methylation sites was correlated with the expression of m RNA of the corresponding gene. The m RNA expression of KRI1 gene corresponding to cg12013757 was related to the prognosis of lung adenocarcinoma. Conclusion: the methylation level of the methylation site of KRI1 gene has an effect on the prognosis of lung adenocarcinoma, and it can be used as a biomarker for the prognosis of lung cancer.
【作者单位】：华中科技大学同济医学院公共卫生学院流行病与卫生统计学系;
【基金】：国家自然科学基金(81172754)
【分类号】：R734.2

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