癌症中甲基化改变对增强子活性的影响

Analysis of the Effect of Methylation Alterations on Enhancer Activity in Cancer

目的 分析识别癌症中甲基化改变对增强子活性的影响。方法 分别从人类增强子数据库FANTOM5、甲基化DNA结合转录因子数据库MeDReaders及分子特征数据库MSigDB中获取增强子、转录因子结合位点及分子通路数据等信息,识别受甲基化影响的活性增强子、正常与癌症差异甲基化增强子和探针,并在CpG Island上注释,根据增强子和基因的共表达情况进一步识别增强子甲基化调控的靶基因并在泛癌模块中进行功能富集分析,最后进行COX比例风险回归分析与功能分析模式的识别。结果 共识别出1 155个受甲基化调控的增强子,其对应的探针大部分是在癌症中表现差异甲基化的探针,少数在癌症中受甲基化调控的增强子所对应的探针没有表现出差异甲基化。根据增强子和基因的共表达筛选出的靶基因和癌症相关通路有关,这些基因还参与到癌症相关(P53通路)、转录相关(transcript通路)、信号转导相关以及代谢相关等重要功能的通路中;在膀胱尿路上皮癌中存在很多三元组合与生存相关,这些靶基因还分布在癌症相关通路以及其他生命健康相关通路中。结论 本研究系统分析了癌症中受甲基化影响的增强子调控,识别了关键的增强子通过调控重要的靶基因参与癌症发生发展的功能。

Objective To analyze and identify the impact of methylation changes on enhancer activity in cancer.Methods Obtain enhancers,transcription factor binding sites,and molecular pathway data from the human enhancer database FANTOM5,methylated DNA binding transcription factor database MeDReaders,and molecular feature database MSigDB,identify active enhancers affected by methylation,normal and cancer differential methylation enhancers,and probes,and annotate them on CpG Island,Based on the co expression of enhancers and genes,further identify the target genes for enhancer methylation regulation and perform functional enrichment analysis in the pan cancer module.Finally,perform COX proportional risk regression analysis and functional analysis pattern recognition.Results A total of 1155 enhancers regulated by methylation were identified,with most of their corresponding probes exhibiting differential methylation in cancer,while a few probes corresponding to enhancers regulated by methylation in cancer did not exhibit differential methylation.The target genes screened based on the co expression of enhancers and genes are related to cancer related pathways,and these genes are also involved in important pathways related to cancer(P53 pathway),transcription(script pathway),signal transduction,and metabolism;There are many ternary combinations associated with survival in bladder urothelial carcinoma,and these target genes are also distributed in cancer related pathways and other life and health related pathways.Conclusion This study systematically analyzed the enhancer regulation affected by methylation in cancer and identified key enhancers involved in the development of cancer by regulating important target genes.