| 摘要: |
| ［摘要］ 目的 应用全基因组甲基化芯片筛选结直肠腺瘤基因启动子区甲基化标志物。方法 选择2013年1月至2014年12月在广西壮族自治区人民医院及广西医科大学第一附属医院住院的进展期结直肠腺瘤患者9例（腺瘤组），另选择经肠镜排除炎症性肠疾病、癌前病变及癌的患者20例作为对照组。腺瘤组于内镜下切除结直肠腺瘤标本（直径≥2 cm），对照组取结直肠黏膜标本（结肠黏膜13例，直肠黏膜7例）。提取组织DNA，应用全基因组甲基化芯片进行甲基化检测，通过生物信息学分析筛选差异甲基化基因启动子区甲基化标志物。结果 以Δβ≥|0.4|，在基因启动子区共发现1 870个差异甲基化标志物，1 524个为高甲基化标志物，346个为低甲基化标志物，其中包含929个启动子差异甲基化基因。GO分析结果显示，启动子差异甲基化基因主要在化学性突触传递、神经系统发育、细胞外基质组织、细胞外基质结构成分、RNA聚合酶Ⅱ调控区序列特异性DNA结合、序列特异性DNA结合、质膜、蛋白质类细胞外基质、细胞膜等注释条目中出现富集。KEGG_Pathyway分析显示，启动子差异甲基化基因主要参与了神经活性的配体-受体相互作用、尼古丁成瘾、钙信号通路等信号转导通路。结论 应用全基因组甲基化芯片筛选结直肠腺瘤甲基化标志物有助于探讨结直肠腺瘤的发病机制，为疾病的早期诊断提供线索。 |
| 关键词: 甲基化标志物 结直肠腺瘤 全基因组甲基化芯片 |
| DOI：10.3969/j.issn.1674-3806.2022.01.08 |
| 分类号:R 735.3 |
| 基金项目:国家自然科学基金项目（编号：81360334） |
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| Screening of methylation markers in gene promoter region of colorectal adenoma using genome-scale methylation chip |
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HE Chun-gang, HUANG Qin-yuan, ZHONG Shi-biao, et al.
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Department of Colorectal and Anal Surgery, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To screen methylation markers in gene promoter region of colorectal adenoma using genome-scale methylation chip. Methods Nine patients with advanced colorectal adenoma(adenoma group) who were hospitalized in the People′s Hospital of Guangxi Zhuang Autonomous Region and the First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2014 were selected. In addition, 20 patients whose inflammatory bowel disease, precancerous lesions and cancer were excluded by colonoscopy were selected as the control group. The colorectal adenoma specimens(diameter ≥2 cm) in the adenoma group were resected under endoscopy, and the colorectal mucosa specimens were taken in the control group(13 cases of colonic mucosa, 7 cases of rectal mucosa). The tissue DNA was extracted and genome-scale methylation chip was used for methylation detection, and the differential methylation markers in gene promoter region were screened by bioinformatics analysis. Results According to Δβ≥|0.4|, a total of 1 870 differential methylation markers were found in the gene promoter region, among which 1 524 were hypermethylation markers, and 346 were hypomethylation markers, including 929 differential promoter methylation genes. The results of GO analysis showed that the differentially methylated genes of promoters were mainly enriched in annotation items such as chemical synaptic transmission, nervous system development, extracellular matrix tissue, extracellular matrix structural components, RNA polymerase Ⅱ regulatory region sequence-specific DNA binding, and sequence-specific DNA binding, plasma membrane, proteinaceous extracellular matrix and cell membrane. KEGG_Pathyway analysis showed that promoter differential methylation genes were mainly involved in signal transduction pathways such as neural activity ligand-receptor interaction, nicotine addiction, calcium signaling pathway, etc. Conclusion Screening the methylation markers of colorectal adenomas using genome-scale methylation chip is helpful to explore the pathogenesis of colorectal adenomas and provide clues for the early diagnosis of the disease. |
| Key words: Methylation markers Colorectal adenoma Genome-scale methylation chip |
