| 杨倩,李颖,王璐,宋志超,冯美娟,丁玲,王金桃.脆性组氨酸三联体、甲基-CpG-结合蛋白2异常表达与宫颈癌变的关系及交互作用[J].中华流行病学杂志,2018,39(5):689-693 |
| 脆性组氨酸三联体、甲基-CpG-结合蛋白2异常表达与宫颈癌变的关系及交互作用 |
| Interaction between abnormal expression of fragile histidine triad and methyl-CpG-binding protein 2 on cervical cancerization |
| 收稿日期:2017-10-17 出版日期:2018-05-24 |
| DOI：10.3760/cma.j.issn.0254-6450.2018.05.030 |
| 中文关键词: 宫颈癌变 脆性组氨酸三联体 甲基-CpG-结合蛋白2 |
| 英文关键词: Cervical carcinogenesis Fragile histidine triad Methyl-CpG-binding protein 2 |
| 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）；山西省优势和特色重点学科建设项目 |
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| 中文摘要: |
| 目的 探讨脆性组氨酸三联体（FHIT）与甲基-CpG-结合蛋白2（MeCP2）异常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73例，宫颈上皮内瘤样变（CIN）患者113例（CINⅠ45例；CINⅡ/Ⅲ68例）和宫颈正常（NC）妇女60人作为研究对象，分别采用荧光定量PCR和Western blot检测宫颈组织中FHIT及MeCP2 mRNA和蛋白的表达量，甲基化特异性PCR（MSP）检测FHIT基因CpG岛甲基化状态。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 随着宫颈癌变的进展，FHIT基因CpG岛甲基化率（χ2=18.64，P<0.001，趋势检验χ2=18.08，P<0.001）逐渐升高，FHIT mRNA（H=27.32，P<0.001；趋势检验χ2=12.65，P<0.001）与蛋白（H=47.10，P<0.001；趋势检验χ2=29.79，P<0.001）表达量逐渐降低，且FHIT基因CpG岛甲基化率与FHIT蛋白表达量呈负相关（r=-0.226，P<0.001）。MeCP2 mRNA（H=26.19，P<0.001；趋势检验χ2=11.81，P=0.001）与蛋白（H=69.02，P<0.001；趋势检验χ2=47.44，P<0.001）表达量均逐渐升高。MeCP2蛋白表达量与FHIT mRNA Ct比值呈正相关（r=0.254，P<0.001），与FHIT蛋白表达量呈负相关（r=-0.213，P=0.001）。GMDR交互作用分析表明，在CINⅡ/Ⅲ组，MeCP2蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达存在交互作用；在SCC组，MeCP2 mRNA和蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达存在交互作用。结论 MeCP2 mRNA和蛋白高表达、FHIT基因CpG岛甲基化及mRNA和蛋白低表达，均可增加宫颈癌变的风险，且在宫颈癌变中具有协同作用。 |
| 英文摘要: |
| Objective To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ2 test, trend χ2 test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ2=18.64, P<0.001; trend χ2=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ2=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ2=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ2=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ2=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis. |
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