文章摘要
李巧玲,丁玲,南晶,刘春亮,杨作凯,陈芳,梁雅丽,王金桃.叶酸与甲基-CpG-结合蛋白2基因表达在宫颈癌变中的关系及交互作用[J].中华流行病学杂志,2016,37(7):985-991
叶酸与甲基-CpG-结合蛋白2基因表达在宫颈癌变中的关系及交互作用
Relationship and interaction between folate and expression of methyl-CpG-binding protein 2 in cervical cancerization
收稿日期:2016-01-15  出版日期:2016-07-15
DOI:10.3760/cma.j.issn.0254-6450.2016.07.016
中文关键词: 叶酸  甲基-CpG-结合蛋白2  宫颈癌变  交互作用
英文关键词: Folate acid  Methyl-CpG-binding protein 2  Cervix carcinogenesis  Interaction
基金项目:国家自然科学基金(30872166,81273157,81473060);国家卫生和计划生育委员会公益性行业科研专项(201402010);山西省自然科学基金(2008011075-1)
作者单位E-mail
李巧玲 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
丁玲 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
南晶 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
刘春亮 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
杨作凯 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
陈芳 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
梁雅丽 030001 太原, 山西医科大学公共卫生学院流行病学教研室  
王金桃 030001 太原, 山西医科大学公共卫生学院流行病学教研室 wangjt59@163.com 
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中文摘要:
      目的 探讨叶酸和甲基-CpG-结合蛋白2(MeCP2)表达在宫颈癌变中的交互作用。方法 选择经病理学确诊的宫颈鳞状细胞癌(SCC)患者41例,宫颈上皮内瘤样变(CIN)患者71例(34例CIN1和37例CIN2+)及61名宫颈正常(NC)妇女为研究对象。采用微生物法检测血清叶酸和红细胞叶酸水平,Western blot法和荧光定量PCR法检测宫颈组织中MeCP2蛋白和mRNA的表达量。利用SPSS 20.0软件进行相关资料的Kruskal-Wallis H检验、χ2检验、χ2趋势检验和Spearman秩相关分析,应用广义多因子降维模型(GMDR)评价交互作用。结果 随着宫颈病变程度的加重,血清叶酸(H=44.71,P<0.001;趋势检验 χ2=24.48,P<0.001)和红细胞叶酸(H=5.28,P<0.001;趋势检验 χ2=3.83,P<0.05)水平均呈逐渐降低趋势,且血清叶酸和红细胞叶酸水平呈正相关(r=0.270,P<0.001);MeCP2蛋白(H=33.72,P<0.001;趋势检验χ2=14.74,P<0.001)和mRNA (H=19.50,P<0.001;趋势检验χ2=10.74,P<0.001)表达量随着宫颈病变的进展均呈逐渐升高趋势;叶酸水平与MeCP2蛋白表达量呈负相关(血清叶酸:r=-0.226,P=0.003;红细胞叶酸:r=-0.164,P=0.004)。GMDR交互作用分析表明,在SCC组和CIN2+组,血清叶酸和红细胞叶酸缺乏,MeCP2蛋白高表达与MeCP2mRNA高表达呈现交互作用。结论 叶酸缺乏和MeCP2基因异常高表达可增加宫颈癌及其癌前病变的风险,血清叶酸缺乏、红细胞叶酸缺乏、MeCP2蛋白高表达和MeCP2mRNA高表达在宫颈癌变的发展过程中具有协同作用。
英文摘要:
      Objective To explore the interaction between folate and the expression of methyl-CpG-binding protein 2 (MeCP2) in cervical cancerization. Methods Forty one patients diagnosed with cervical squamous cell carcinoma (SCC), 71 patients diagnosed with cervical intraepithelial neoplasm (CIN1, n=34; CIN2+, n=37) and 61 women with normal cervix (NC) were recruited in this study. Microbiological assay was conducted to detect the levels of serum folate and RBC folate, Western blot assay and real-time PCR were performed to detect the expression levels of MeCP2 protein and mRNA, respectively. The data were analyzed by Kruskal-Wallis H test, χ2 test, trend χ2 test and Spearman correlation with SPSS statistical software (version 20.0), and the interaction were evaluated by using generalized multifactor dimensionality reduction (GMDR) model. Results The levels of serum folate (H=44.71, P<0.001; trend χ2=24.48, P<0.001) and RBC folate (H=5.28, P<0.001; trend χ2=3.83, P<0.05) decreased gradually along with the severity of cervical lesions. There was a positive correlation between serum folate level and RBC folate level (r=0.270, P<0.001). The expression levels of MeCP2 protein (H=33.72, P<0.001; trend χ2=14.74, P<0.001) and mRNA (H=19.50, P<0.001; trend χ2=10.74, P<0.001) increased gradually along with the severity of cervical lesions. There were negative correlation between folate level and the expression level of MeCP2 protein (serum folate:r=-0.226, P=0.003; RBC folate:r=-0.164, P=0.004). Moreover, the results by GMDR model revealed there were interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and MeCP2 mRNA high expression in SCC and CIN2+patients. Conclusion Folate deficiency and high expression of MeCP2 gene might increase the risk of cervical cancer and its precancerous lesions through interaction among serum folate deficiency, RBC folate deficiency, MeCP2 protein high expression and mRNA high expression in the progression of cervical cancerization.
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