DNA甲基转移酶1与甲基-CpG-结合蛋白2异常表达在宫颈病变中的作用及相互关系

康慧杰; 王金桃; 高晨菲; 白丽霞; 丁玲; 许娟; 吴婷婷; 白兰

Abstract

康慧杰,王金桃,高晨菲,白丽霞,丁玲,许娟,吴婷婷,白兰.DNA甲基转移酶1与甲基-CpG-结合蛋白2异常表达在宫颈病变中的作用及相互关系[J].Chinese journal of Epidemiology,2013,34(12):1223-1227

DNA甲基转移酶1与甲基-CpG-结合蛋白2异常表达在宫颈病变中的作用及相互关系

Effect of DNA methyltransferase 1 and methyl.CpG.binding protein 2 abnormal expression ollcervical lesions and related interaction

Received:July 18, 2013

DOI：10.3760/cmaj.issn.0254-6450.2013.012.016

KeyWord: 宫颈肿瘤宫颈癌前病变 DNA甲基转移酶l 甲基一CPG一结合蛋白2

English Key Word: Cervical neoplasms Cervix precancerous lesion DNA methyltransferase 1 Methyl-CpG-binding protein 2

FundProject:国家自然科学基金(30872166,81273157);山西省自然科学基金(2008011075一1)

Author Name	Affiliation	E-mail
Kang Huijie	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Wang Jintao	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China	wangjt59@163.com
Gao Chenfei	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Bai Lixia	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Ding Ling	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Xu Juan	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Wu Tingting	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China
Bailan	Department of Epidemiology,School of Public Health, Shanxi Medical Urziversity, Taiyuan 030001,China

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Abstract:

目的探讨DNA甲基转移酶1(DNMTl)和甲基-CPG-结合蛋白2(MecP2)与宫颈癌发生发展的关系及其在宫颈癌变中的相互作用。方法选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者74例、低度宫颈上皮内瘤样变(CIN I)患者52例、高度宫颈上皮内瘤样变(CINⅡ一Ⅲ)患者60例和宫颈炎(CI)患者58例为研究对象。在收集全部对象人口学特征、人乳头瘤病毒感染、生殖因素等相关资料同时,检测DNMTl和MeCP2蛋白(Western blot法)和mRNA(real-time PCR法)的相对表达量。采用SPSS 17.0分析软件,计算相关资料的t检验、X²检验、因素与疾病之间关联强度指标(0R值及其95%CI)及其交互作用。结果随着宫颈病变的加重,DNMTl和MeCP2蛋白表达水平逐渐增高(H=94.33,PF=21.580,P<0.001),DNMTl和MeCP2 mRNA的表达水平亦逐渐增高(F=4.758,P=0.003；F=7。804,Pr=0.287,P<0.001)和mRNA(r=0.179,P=0.005)表达均存在正相关关系。交互作用分析显示,DNMTl与MeCP2蛋白和mRNA高表达在SCC组和CINl/-Ⅲ组存在正相加交互作用。结论 DNMTl及MeCP2高表达可增加宫颈癌和癌前病变发生的风险,两者在C1N II-Ⅲ组和SCC组存在正相加交互作用。

English Abstract:

0bjeetive To explore the effect of DNA methyltransferase 1(DNMTl)andmethyl.CpG.binding protein 2(MeCP2)on cervical cancer and cervix precancerous 1esion.Methods 74 patients with cervix squamous eell carcinoma(SCC).52 patients with cervicalintraepithelial neoplasm I(CIN I).60 patients with cervical intraepithelial neoplasmⅡ-III(CIN II-HI)and 58 patients with histologically diagnosed cervix inflammation(CI)，were includedin this study.Information as demography，reproductive history，1ife style，HPV infection werecollected.Western Blot were used to detect the expression of DNMT l protein and MeCP2 protein.Real-time PCR was used to detect the expression of DNMT l and MeCP2 mRNA.Results Levels ofDNMTl and MeCP2 protein expression increased gradually with the deterioration of cervical lesion(H=94.33，P<0.00l；F<./i>=21.580，Jp<0.0001AlongwiththedeteriorationofcervicallesionlevelsofDNMTlandMeCP2mRNAexpressionweregraduallyincreasing(F=4.758，P=0.003：F=7.804，P<0.001).Data from Correlation analysis showed that both protein(r=0.287.P<0.001)andmRNA(r=0.179.P=0.005)were positive correlatedwith DNMTl and MeCP2.Results ofour studyindicated that there was an additive interaction between high-expression of DNMTl protein andhigh-expression of MeCP2 protein in SCC or CINⅡ-Ⅲ.However.there was an additive interactionbetween high-expression of DNMTl mRNA and high.expression of MeCP2 mRNA in SCC orCINⅡ-Ⅲ.Conclusion Results from our study revealed the fact that both high expression ofDNMTl protein and high expression of MeCP2 protein could increase the risk of cervix cancerization.According to our findings.there might be a synergistic action existed between DNMTl and MeCP2during the progression ofcervix canceration.

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