肺腺癌患者差异甲基化区域分析

目的探讨DNA甲基化在肺腺癌发生中的作用机制。方法收集2019年1月至12月新疆肿瘤医院确诊的肺腺癌和正常对照者外周血各4例,850K芯片甲基化检测平台检测肺腺癌组与正常对照组甲基化区域,Bump hunter寻找两组差异区域。Gene Ontology数据库和KOBAS软件对差异区域对应目的基因进行GO分析和KEEG分析。结果1.共筛选出DMR-1、DMR-2、DMR-3、DMR-4、DMR-6(以上位于chr6),DMR-5(位于chr11)和DMR-7(位于chr20)(P<0.05)七组差异甲基化区域。DMR-1目的基因为HLA-DPB1、HLA-DPA1,DMR-2的为POU5F1,DMR-3的为RP5-1186N24.3、SCAND3,DMR-4的为ZFP57,DMR-5的为LDHC,DMR-6的为LTA,DMR-7的为OXT。其中HLA-DPB1、HLA-DPA1等为高甲基化,SCANDS3和LTA为低甲基化。2.GO分析表明目的基因主要在干扰素-γ、MHC-Ⅱ类复合物等功能中发挥重要作用。KEGG分析显示目的基因甲基化主要在Ⅰ型糖尿病、NF-κB信号通路中高度富集。结论1.肺腺癌患者DNA甲基化的状态可能是引起肺腺癌发生的关键因素,尤其是HLA-DP,POU5F1及LDHC的甲基化状态,在肺腺癌的发生中起着重要的作用。2.在GO功能和KEGG通路中,阐明了DNA甲基化异常导致疾病发展的作用机制。

Analysis of differentially methylated regions in patients with lung adenocarcinoma

Objective To explore the underlying mechanism of DNA methylation in the occurrence of lung adenocarcinoma.Methods From January to December 2019,peripheral blood samples from 4 lung adenocarcinoma patients diagnosed in Xinjiang Cancer Hospital and 4 healthy controls were collected.Using 850K chip methylation detection platform to detect the methylation area of lung adenocarcinoma group and normal control group.Bump hunter was used to looking for the different areas of the two groups.The Gene Ontology database and KOBAS software were used for GO analysis and KEEG analysis on the target genes corresponding to the different regions.Results 1.A total of seven sets of differentially methylated regions were screened out:DMR-1,DMR-2,DMR-3,DMR-4,DMR-6(above in chr6),DMR-5(in chr11),and DMR-7(in chr20)(P<0.05).DMR-1 target genes were HLA-DPB1 and HLA-DPA1,DMR-2 was POU5F1,DMR-3 were RP5-1186N24.3 and SCAND3,DMR-4 was ZFP57,DMR-5 was LDHC,DMR-6 was LTA,and DMR-7 was OXT.Among them,HLA-DPB1 and HLA-DPA1 were hypermethylated,while SCANDS3 and LTA were hypomethylated.2.GO analysis showed that the target genes mainly play an important role in the functions of interferon-γand MHC-Ⅱcomplex.KEGG analysis showed that the target genes methylation were highly enriched in type I diabetes and NF-κB signaling pathway.Conclusion 1.The DNA methylation status of patients with lung adenocarcinoma may be the key factor causing the occurrence of lung adenocarcinoma,especially the methylation status of HLA-DP,POU5F1 and LDHC play an important role in the occurrence of lung adenocarcinoma.2.In the GO function and KEGG pathway,the mechanism of abnormal DNA methylation leading to disease development was clarified.