癌变·畸变·突变
癌變·畸變·突變
암변·기변·돌변
CARCINOGENSES,TERATOGENSIS AND MUTAGENESIS
2014年
2期
94-99
,共6页
DNA甲基化%食管癌%哈萨克族%生物信息学分析
DNA甲基化%食管癌%哈薩剋族%生物信息學分析
DNA갑기화%식관암%합살극족%생물신식학분석
DNA methylation%ESCC%Kazakh ethnic group%bioinformmatic analysis
目的：筛选新疆哈萨克族食管鳞癌DNA异常甲基化谱，为深入研究食管癌的发生机制提供线索。方法：采用Illumina Human Methylation 450K甲基化芯片，对6例哈萨克族食管癌组织及其癌旁正常组织进行全基因组甲基化检测，筛选DNA异常甲基化基因；利用Hiseq2000测序平台，对2例哈萨克族食管癌组织及其癌旁正常组织进行RNA水平检测，建立mRNA文库，并与DNA 甲基化结果进行关联分析，筛选DNA异常甲基化谱，同时对这些基因进行生物信息学分析。结果：食管癌组织中含高甲基化基因227个，低甲基化基因6个；癌组织mRNA表达量在0.0312～8192，癌旁正常组织在0.0312～1024。DNA异常甲基化基因与表达谱关联分析，呈负相关关系(即DNA高甲基化、mRNA低表达，或DNA低甲基化、mRNA高表达)的启动子区域基因共20个，包括启动子区域CpG岛高甲基化且表达下调10个位点、10个基因，低甲基化且表达上调11个位点、10个基因。生物信息学分析表明这些基因参与甲酰四氢叶酸分解代谢及调控细胞增殖等生物学过程，涉及一碳代谢通路及诱导细胞凋亡通路等。结论：初步建立了新疆哈萨克族食管癌DNA 异常甲基化谱，为哈萨克族食管癌的发病机制研究提供了新的思路。
目的：篩選新疆哈薩剋族食管鱗癌DNA異常甲基化譜，為深入研究食管癌的髮生機製提供線索。方法：採用Illumina Human Methylation 450K甲基化芯片，對6例哈薩剋族食管癌組織及其癌徬正常組織進行全基因組甲基化檢測，篩選DNA異常甲基化基因；利用Hiseq2000測序平檯，對2例哈薩剋族食管癌組織及其癌徬正常組織進行RNA水平檢測，建立mRNA文庫，併與DNA 甲基化結果進行關聯分析，篩選DNA異常甲基化譜，同時對這些基因進行生物信息學分析。結果：食管癌組織中含高甲基化基因227箇，低甲基化基因6箇；癌組織mRNA錶達量在0.0312～8192，癌徬正常組織在0.0312～1024。DNA異常甲基化基因與錶達譜關聯分析，呈負相關關繫(即DNA高甲基化、mRNA低錶達，或DNA低甲基化、mRNA高錶達)的啟動子區域基因共20箇，包括啟動子區域CpG島高甲基化且錶達下調10箇位點、10箇基因，低甲基化且錶達上調11箇位點、10箇基因。生物信息學分析錶明這些基因參與甲酰四氫葉痠分解代謝及調控細胞增殖等生物學過程，涉及一碳代謝通路及誘導細胞凋亡通路等。結論：初步建立瞭新疆哈薩剋族食管癌DNA 異常甲基化譜，為哈薩剋族食管癌的髮病機製研究提供瞭新的思路。
목적：사선신강합살극족식관린암DNA이상갑기화보，위심입연구식관암적발생궤제제공선색。방법：채용Illumina Human Methylation 450K갑기화심편，대6례합살극족식관암조직급기암방정상조직진행전기인조갑기화검측，사선DNA이상갑기화기인；이용Hiseq2000측서평태，대2례합살극족식관암조직급기암방정상조직진행RNA수평검측，건립mRNA문고，병여DNA 갑기화결과진행관련분석，사선DNA이상갑기화보，동시대저사기인진행생물신식학분석。결과：식관암조직중함고갑기화기인227개，저갑기화기인6개；암조직mRNA표체량재0.0312～8192，암방정상조직재0.0312～1024。DNA이상갑기화기인여표체보관련분석，정부상관관계(즉DNA고갑기화、mRNA저표체，혹DNA저갑기화、mRNA고표체)적계동자구역기인공20개，포괄계동자구역CpG도고갑기화차표체하조10개위점、10개기인，저갑기화차표체상조11개위점、10개기인。생물신식학분석표명저사기인삼여갑선사경협산분해대사급조공세포증식등생물학과정，섭급일탄대사통로급유도세포조망통로등。결론：초보건립료신강합살극족식관암DNA 이상갑기화보，위합살극족식관암적발병궤제연구제공료신적사로。
OBJECTIVE: To screen the aberrant methylation genes in esophageal squamous cell carcinoma for Kazakh ethnic group in Xinjiang. The aberrant methylation pattern would provide a clue for in-depth study on esophageal squamous cell carcinoma mechanism.METHODS:We used Illumina Human Methylation 450K chip to carry out the genome-wide methylation screening on 6 cancer tissues and 6 adjacent normal tissues of esophageal squamous cell carcinoma in Kazakh people, to explore aberrant the methylation genes. Genome-wide sequencing were carried out on 2 cancer tissues and 2 adjacent normal tissues by Hiseq2000. Meanwhile,mRNA database was established. With the association study between the methylation profile and expression profile,aberrant DNA methylation genes were identifed and were uploaded to the GoMiner and the KEGG database,completing the bioinformatic analysis. RESULTS:There were 227 hypermethylated genes and 6 hypomethylated genes in cancer tissue,mRNA expression varied from 0.031 2 to 8 192 in cancer tissues and from 0.031 2 to 1 024 in adjacent normal tissues. The association study indicated that there were 10 loci,10 down-regulated genes hypermethylated in promoter region in the negative group. Additionally,there were 11 loci,10 up-regulated genes in the negative group. Using GoMiner to do GO analysis on aberrant DNA methylation genes,revealed that ALDH1L1 ralated to folinic acid catabolism and CAPN1 was associated with positive regulation of cell proliferation. During pathyway analysis,we found that ALDH1L1 was involved in one carbon metabolism and CAPN1 participated in the apoptosis process. CONCLUSION:The aberrant DNA methylation profiles were estabilsed and provided a clue for further studies on ESCC of Kazakh ethnic group.
