李晓晗,曹国磊,牛海文,等.差异甲基化区域与肺腺癌发生发展的关系[J].肿瘤学杂志,2022,28(7):574-578.
差异甲基化区域与肺腺癌发生发展的关系
Relationship of Differentially Methylated Regions with Lung Adenocarcinoma
投稿时间:2021-11-15  
DOI:10.11735/j.issn.1671-170X.2022.07.B008
中文关键词:  肺腺癌  DNA甲基化  基因表达  生物信息学
英文关键词:lung adenocarcinoma  DNA methylation  gene expression  bioinformatics
基金项目:国家自然科学基金(81760014);新疆自治区科技支疆项目计划(2019E0281)
作者单位
李晓晗 新疆医科大学第三临床医学院 
曹国磊 新疆医科大学附属肿瘤医院 
牛海文 新疆医科大学第三临床医学院 
何丽丽 新疆医科大学附属肿瘤医院 
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中文摘要:
      摘 要:[目的] 探讨差异化甲基区域与肺腺癌发生发展的关系。[方法] 收集新疆医科大学附属肿瘤医院2019年1—12月肺腺癌患者及健康对照组外周血各4例,采用Illumina高通量测序平台和850K芯片甲基化检测平台分别检测8例外周血基因谱数据,并以P<0.05为标准筛选差异表达基因(differentially expressed genes,DEGs)及差异甲基化区域,进一步行DNA甲基化-基因表达联合分析得到目的基因。[结果] 筛选出1 111个有意义的DEGs;针对DEGs各个区段甲基化的情况,筛选出4 519个差异甲基化基因,对比各组DNA甲基化和组间差异表达的全部基因,筛选出显著性差异表达基因和差异甲基化的基因,筛选得到6个目的基因,即CCR7、CD27、DSC1、LEF1-AS1、SLC8A1和LRRN3。GO功能分析显示差异甲基化区域在生物学途径、细胞成分和分子功能等方面密切相关。在GO功能和KEGG通路中,肺癌发生可能涉及CCL19和CCL21信号通路、缝隙连接、桥粒等分子机制,以及参与cGMP·PKG信号通路及钙离子信号通路等相关通路。[结论] CCR7、CD27、DSC1等甲基化的状态以及NFKB1-CCR7、STAT3-DSC1、SP1-CCR7等转录因子-基因表达调控网络可能参与肺癌的发生发展;差异甲基化区域在JNK通路及钙离子等信号通路中发挥着重要作用。
英文摘要:
      Abstract: [Objective] To investigate the relationship of differentially methylated regions with lung adenocarcinoma. [Methods] Peripheral blood samples were collected from 4 patients with lung adenocarcinoma and 4 healthy controls in the Affiliated Cancer Hospital of Xinjiang Medical University from January 2019 to December 2019. Illumina high-throughput sequencing platform and 850K chip(Illumina Infinium MethylationEPIC BeadChip chip) and methylation detection platform were used to detect the peripheral blood gene profile. The differentially expressed genes(DEGs) and differentially methylated regions were screened when P<0.05. Further DNA methylation-gene expression combined analysis was performed to obtain the target gene. [Results] A total of 1 111 significant DEGs and 4 519 differentially methylated genes were screened out, the genes with DNA methylation and differential expression were compared between two groups. Six significantly differentially expressed genes and significantly differentially methylated genes were identified, namely CCR7, CD27, DSC1, LEF1-AS1, SLC8A1, and LRRN3. Gene Ontology analysis of target gene showed that these genes were closely related in biological pathways, cellular components and molecular functions. KEGG pathway indicated their roles in signaling pathways such as cGMP·PKG pathway and calcium ions. [Conclusion] The methylation status of CCR7, CD27, DSC1, NFKB1-CCR7, STAT3-DSC1, SP1-CCR7 and other transcription factor-gene expression regulatory networks may be involved in the occurrence and development of lung cancer; diffientially methylated regions have important role in JNK signaling pathway and calcium ions signaling pathway and other related pathways.
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