肝癌组织中HBV感染与甲基化转移酶表达的关系

张吉才; 余宗涛; 吕军; 李海平; 高波

doi:10.3969/j.issn.1001-5256.2013.08.017

肝癌组织中HBV感染与甲基化转移酶表达的关系

DOI: 10.3969/j.issn.1001-5256.2013.08.017

湖北医药学院附属太和医院检验科

基金项目:

湖北省教育厅重大项目资助(Z20082401)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 2935
- HTML全文浏览量: 18
- PDF下载量: 629
- 被引次数: 0
出版历程
- 收稿日期: 2012-11-06
- 出版日期: 2013-08-20

Relationship between HBV infection and DNMT expression in liver cancer tissues

Research funding:

摘要

摘要:
目的检测肝癌患者癌组织、肝癌旁组织、肝硬化相关组织中甲基化转移酶（DNMT）的表达情况,分析HBV感染与DN-MT表达之间的关系。方法根据是否存在HBV感染,将44例标本分成两组。HBV感染相关组:血液或组织中至少可检测出一种HBV感染相关的标志物;非HBV感染相关组:血液或组织中未检测出HBV感染相关标志物。应用荧光定量PCR（FQ-PCR）检测分期及分化程度不同的肝癌患者癌组织、肝癌旁组织、肝硬化组织中DNMT基因mRNA的表达水平。不同组间DNMTs表达水平的差异采用ANOVA分析;非参数检验方法为Spearman等级相关分析。结果 HBV感染相关组中癌组织的DNMT1、3A和3B mRNA表达水平明显高于非HBV感染相关组（P=0.001、0.006、0.02）;HBV感染相关组中肝硬化组织的DNMT1、3A和3B mRNA表达水平也明显高于非HBV感染相关组（P=0.007、0.008、0.045）;即使在癌旁组织,HBV感染相关组织中DNMT1、3A mRNA表达水平明显高于非HBV感染相关组织（P=0.01、0.04）。HBV感染与DNMTs表达相关分析结果显示:HBV感...
- 肝肿瘤 /
- 甲基转移酶类 /
- 肝炎病毒,乙型 /
- 基因表达
Abstract:
Objective To investigate the expression of DNA methyltransferases (DNMTs) in cancerous tissues, paracancerous tissues, and cirrhotic tissues among patients with liver cancer and to analyze the relationship between HBV infection and DNMT expression.Methods Forty-four samples were divided into HBV infection group and non-HBV infection group according to whether at least one marker of HBV infection could be detected in blood or tissue.FQ-PCR was used to measure the mRNA expression levels of DNMTs in the cancerous tissues, paracancerous tissues, and cirrhotic tissues with different tumor stages and differentiations.The differences in DNMT expression between groups were determined by analysis of variance;the relationship between HBV infection and DNMT expression was evaluated by Spearman rank correlation analysis.Results Compared with the non-HBV infection group, the HBV infection group had significantly higher mRNA expression levels of DNMT1, 3A, and 3B in cancerous tissues (P=0.001, 0.006, and 0.02) and in cirrhotic tissues (P=0.007, 0.008, and 0.045) and significantly higher mRNA expression levels of DNMT1 and 3A in paracancerous tissues (P=0.01 and 0.04) .There were significant associations between HBV infection and DNMT expression (P=0.009 for DNMT1, 0.006 for DNMT3A, and 0.03 for DNMT3B) ;HBsAg, HBeAg, and HBV-DNA were closely related to DNMT1 expression (P=0.008, 0.032, and 0.006) .Conclusion The liver cancer patients with HBV infection have significantly higher mRNA expression levels of DNMT1, 3A, and 3B in cancerous and cirrhotic tissues than those without HBV infection.HBV infection may stimulate the expression of DNMTs, especially DNMT1, 3A, and 3B, thus promoting methylation of some tumor-suppressor genes.
- liver neoplasms /
- methyltransferases /
- hepatitis B virus /
- gene expression

HTML全文

参考文献(13)

[1]LI HP, ZHANG JC, FENG J, et al.Detection of promoter hyperm-ethylation and mRNA expression of 14-3-3σGene in tissues ofhuman hepatocellular carcinoma[J].Cancer Res Prevent Treat, 2008, 35 (8) :572-575. (in Chinese) 李海平, 张吉才, 冯景, 等.肝癌组织中14-3-3σ启动子异常甲基化及基因转录水平检测[J].肿瘤防治研究, 2008, 35 (8) :572-575.

[2]YANG XX, SUN JZ, LI FX, et al.Aberrant methylation and down-regulation of sall3 in human hepatocellular carcinoma[J].World JGastroenterol, 2012, 18 (21) :2719-2726.

[3]HUA D, HU Y, WU YY, et al.Quantitative methylation analysis ofmultiple genes using methylation-sensitive restriction enzyme-basedquantitative PCR for the detection of hepatocellular carcinoma[J].ExpMol Pathol, 2011, 91 (1) :455-460.

[4] ZHANG JC, YU ZT, LYU J, et al.Persistent infection of hepatitis Bvirus is involved in high rate of p16 methylation in hepatocellular carci-noma[J].Mol Carcinog, 2006, 45 (7) :530-536.

[5]ZHANG JC, LYU J, LI HP, et al.p16 promoter hypermethylationin the plasma DNA and its possible application in molecular diagno-sis of hepatocellular carcinoma[J].Chin J Lab Med, 2006, 29 (10) :895-898. (in Chinese) 张吉才, 吕军, 李海平, 等.血浆p16启动子异常甲基化在肝癌诊断中的应用价值[J].中华检验医学杂志, 2006, 29 (10) :895-898.

[6]ZHANG JC, YU ZT, LYU J, et al.Hepatitis B virus enhance themethylation of CDKN2A in hepatocellular carcinoma[J].Chin J CancerPrevent Treat, 2006, 13 (12) :892-895. (in Chinese) 张吉才, 余宗涛, 吕军, 等.HBV感染与肝癌组织CDKN2A基因甲基化关系的研究[J].中华肿瘤防治杂志, 2006, 13 (12) :892-895.

[7] LU ZY.Medcine[M].Beijing:People's Medical PublishingHouse, 2008:467. (in Chinese) 陆再英.内科学[M].北京:人民卫生出版社, 2008:467.

[8]LAI HJ, LO SJ.Epigenetic methylation of TIMP-3 may play a rolein HBV-associated hepatocellular carcinoma[J].Chang GungMed J, 2005, 28 (7) :453-455.

[9]LAMBERT MP, PALIWAL A, VAISSIèRE T, et al.Aberrant DNAmethylation distinguishes hepatocellular carcinoma associated with HBVand HCV infection and alcohol intake[J].J Hepatol, 2011, 54 (4) :705-715.

[10]TSAI CN, TSAI CL, TSE KP, et al.The Epstein-Barr virus onco-gene product, latent membrane protein 1, induces the downregula-tion of E-cadherin gene expression via activation of DNA methyl-transferases[J].PNAS, 2002, 99 (15) :10084-10089.

[11]ETOH T, KANAI Y, USHIJIMA S, et al.Increased DNA Methyltrans-ferase 1 (DNMT1) protein expression correlates significantly with poo-rer tumor differentiation and frequent DNA hypermethylation of multipleCpG islands in gastric cancers[J].Am J Pathol, 2004, 164 (2) :689-699.

[12]FANG JY, LU R, MIKOVITS JA, et al.Regulation of hMSH2 andhMLH1 expression in the human colon cancer cell line SW1116 byDNA methyltransferase 1[J].Cancer Lett, 2006, 233 (1) :124, 130.

[13]ROBERTSON KD, UZVOLGYI E, LIANG G, et al.The humanDNA methyltransferases (DNMTs) 1, 3a and 3b:coordinate mR-NA expression in normal tissues and overexpression in tumors[J].Nucleic Acids Res, 1999, 27 (11) :2291, 2298.

施引文献

资源附件(0)

访问统计