中国医科大学学报

中国医科大学学报
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中国医科大学学报 ›› 2017, Vol. 46 ›› Issue (12): 1111-1116.doi: 10.12007/j.issn.0258-4646.2017.12.012

• 论著 • 上一篇    下一篇

人肝细胞癌细胞DNA甲基化谱的检测及分析

孙宁, 张佳林, 张城硕, 周翔宇, 陈保民   

  1. 中国医科大学附属第一医院肝胆外科暨器官移植科, 沈阳 110001
  • 收稿日期:2017-03-28 出版日期:2017-12-30 发布日期:2017-12-08
  • 通讯作者: 张佳林 E-mail:jlzcmu@126.com
  • 作者简介:孙宁(1986-),女,医师,博士.
  • 基金资助:
    沈阳市科学技术计划(F13-F13-212-9-00)

Exploring Genome-wide Profiles of DNA Methylation in Human Hepatocellular Carcinoma Cells via Bioinformatics Analysis

SUN Ning, ZHANG Jialin, ZHANG Chengshuo, ZHOU Xiangyu, CHEN Baomin   

  1. Department of Hepatobiliary and Transplantation Surgery, The First Hospital, China Medical University, Shenyang 110001, China
  • Received:2017-03-28 Online:2017-12-30 Published:2017-12-08

摘要: 目的 检测人肝细胞癌细胞的DNA甲基化谱,明确肝细胞癌细胞中差异甲基化位点和基因的表达分布情况,进一步探讨DNA异常甲基化与肝细胞癌发生发展的关系。方法 使用DNA甲基化芯片(Infinium Human Methylation 450K BeadChip)检测人肝细胞癌细胞Huh7和人永生化肝细胞L02的甲基化谱,并对检测结果进行生物学分析。结果 共检测到差异性甲基化位点102 254个,差异性甲基化基因26 511个,甲基化相关信号通路43个,其中57.3%的高甲基化CpG位点和39.4%的低甲基化CpG位点的甲基化差异程度≥ 50%,筛选后确定了3 222个显著高甲基化基因和2 204个显著低甲基化基因。结论 在Huh7和L02细胞中存在大量差异性甲基化CpG位点及基因,Huh7细胞中可检测到大量抑癌基因DNA的异常高甲基化,提示DNA异常甲基化与肝细胞癌的发生发展密切相关。

关键词: 肝细胞癌, 甲基化谱, 生物信息学分析

Abstract: Objective To detect the genome-wide profiles of DNA methylation in human hepatocellular carcinoma (HCC) cells and to identify the distribution of differentially methylated sites and genes in order to explore the relationship between aberrant DNA methylation and hepatocellular carcinoma. Methods The Infinium Human Methylation 450K BeadChip was used to identify the genome-wide aberrant DNA methylation profiles in Huh7 and L02 cell lines. Results Totally 102 254 differentially methylated CpG sites and 26 511 genes,involving 43 signaling pathways,were detected when Huh7 and L02 cell lines were compared. The absolute β-difference in 57.3% of the hypermethylated CpG sites and 39.4% of the hypomethylated CpG sites was reported to be ≥ 50%. A total of 3 222 hypermethylated genes and 2 204 hypomethylated genes were identified. Conclusion We detected many aberrant methylated sites and genes in HCC cells. The abnormal DNA methylation exhibits an important role in the occurrence and development of HCC.

Key words: hepatocellular carcinoma, methylation profiles, bioinformatics analysis

中图分类号: 

  • R735.7
[1] CHEN W,ZHENG R,BAADE PD,et al. Cancer statistics in China,2015[J]. CA Cancer J Clin,2016,66(2):115-132. DOI:10.3322/caac.21338.
[2] KULIS M,ESTELLER M. DNA methylation and cancer[J]. Adv Genet,2010,70:27-56. DOI:10.1016/B978-0-12-380866-0.60002-2.
[3] HERMAN JG,BAYLIN SB. Gene silencing in cancer in association with promoter hypermethylation[J]. N Engl J Med,2003,349(21):2042-2054. DOI:10.1056/NEJMra023075.
[4] ESTELLER M. Epigenetic gene silencing in cancer:the DNA hypermethylome[J]. Hum Mol Genet,2007,16(1):R50-R59. DOI:10.1093/hmg/ddm018.
[5] BIBIKOVA M,LE J,BARNES B,et al. Genome-wide DNA methylation profiling using Infinium(R) assay[J]. Epigenomics,2009,1(1):177-200. DOI:10.2217/epi.09.14.
[6] JONES P A,TAKAI D. The role of DNA methylation in mammalian epigenetics[J]. Science,2001,293(5532):1068-1070. DOI:10.1126/science.1063852.
[7] ESTELLER M. Epigenetics in cancer[J]. N Engl J Med,2008,358(11):1148-1159. DOI:10.1056/NEJMra072067.
[8] BIBIKOVA M,BARNES B,TSAN C,et al. High density DNA methylation array with single CpG site resolution[J]. Genomics,2011,98(4):288-295. DOI:10.1016/j.ygeno.2011.07.007.
[9] GAO W,KONDO Y,SHEN L,et al. Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas[J]. Carcinogenesis,2008,29(10):1901-1910. DOI:10.1093/carcin/bgn170.
[10] SHIN SH,KIM BH,JANG JJ,et al. Identification of novel methylation markers in hepatocellular carcinoma using a methylation array[J]. J Korean Med Sci,2010,25(8):1152-1159. DOI:10.3346/jkms.2010.25.8.1152.
[11] AMMERPOHL O,PRASTCHKE J,SCHAFMAYER C,et al. Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma[J]. Int J Cancer,2012,130(6):1319-1328. DOI:10.1002/ijc.26136.
[12] KOHLES N,NAGEL D,JUNGST D,et al. Prognostic relevance of oncological serum biomarkers in liver cancer patients undergoing transarterial chemoembolization therapy[J]. Tumour Biol,2012,33(1):33-40. DOI:10.1007/s13277-011-0237-7.
[13] YATES DR,REHMAN I,MEUTH M,et al. Methylational urinalysis:a prospective study of bladder cancer patients and age stratified benign controls[J]. Oncogene,2006,25(13):1984-1988. DOI:10.1038/sj.onc.1209209.
[14] DUZIEC E,MIAH S,CHOUDHRY HM,et al. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer,clinical cancer research[J]. Clin Cancer Res,2011,17(6):1287-1296. DOI:10.1158/1078-0432.CCR-10-2017.
[15] DOI A,PARK IH,WEN B,et al. Differential methylation of tissue-and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells,embryonic stem cells and fibroblasts[J]. Nat Genet,2009,41(12):1350-1353. DOI:10.1038/ng.471.
[16] IRIZARRY RA,LADD-ACOSTA C,WEN B,et al. The human colon cancer methylome shows similar hypo-and hypermethylation at conserved tissue-specific CpG island shores[J]. Nat Genet,2009,41(2):178-186. DOI:10.1038/ng.298.
[17] OGOSHI K,HASHIMOTO S,NAKATANI Y,et al. Genome-wide profiling of DNA methylation in human cancer cells[J]. Genomics,2011,98(4):280-287. DOI:10.1016/j.ygeno.2011.07.003.
[18] KUO KK,JIAN SF,LI YJ,et al. Epigenetic inactivation of transforming growth factor-beta1 target gene HEYL,a novel tumor suppressor,is involved in the P53-induced apoptotic pathway in hepatocellular carcinoma[J]. Hepatol Res,2015,45(7):782-793. DOI:10.1111/hepr.12414.
[19] UMER M,QURESHI SA,HASHMI ZY,et al. Promoter hypermethylation of Wnt pathway inhibitors in hepatitis C virus-induced multistep hepatocarcinogenesis[J]. Virol J,2014,11:117. DOI:10.1186/1743-422X-11-117.
[20] DING SL,YANG ZW,WANG J,et al. Integrative analysis of aberrant Wnt signaling in hepatitis B virus-related hepatocellular carcinoma[J]. World J Gastroenterol,2015,21(20):6317-6328. DOI:10.3748/wjg.v21.i20.6317.
[21] STEFANSKA B,CHEISHVILI D,SUDERMAN M,et al. Genome-wide study of hypomethylated and induced genes in patients with liver cancer unravels novel anticancer targets[J]. Clin Cancer Res,2014,20(12):3118-3132. DOI:10.1158/1078-0432.CCR-13-0283.
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