子宫内膜腺癌组织中IGFBP？？rP1基因的甲基化状态及其mRNA、蛋白表达水平的检测
Detection of methylation of IGFBP？？rP1 gene and relationship with its mRNA and protein expressions in endometrial adenocarcinoma tissue

目的：探讨子宫内膜腺癌组织中胰岛素样生长因子结合蛋白相关蛋白1(IGFBP？？rP1)基因的甲基化状态及其与IGFBP？？rP1 mRNA、蛋白表达之间的关系。方法：采用甲基化特异性PCR检测45例子宫内膜腺癌、30例子宫内膜单纯性增生和30例子宫内膜不典型增生组织中IGFBP？？rP1基因启动子区和第一外显子区CpG岛的甲基化状态；采用实时荧光定量PCR和免疫组化SP法分别检测上述3种组织中IGFBP？？rP1 mRNA和蛋白的表达。结果：子宫内膜腺癌组织中IGFBP？？rP1基因在启动子区的甲基化率高于其在第一外显子区的甲基化率(χ2=6.429，P=0.011)。子宫内膜腺癌组织中IGFBP？？rP1基因在启动子区的甲基化率低于子宫内膜不典型增生组织和单纯性增生组织(F=14.659，P=0.001)。子宫内膜腺癌组织中IGFBP？？rP1 mRNA和蛋白的表达均高于子宫内膜不典型增生组织和单纯性增生组织（F=8.619、χ2=23.611，P均<0.05）；在启动子区发生IGFBP？？rP1基因甲基化的子宫内膜腺癌组织中，其mRNA的表达水平低于未甲基化组（t=4.758,P=0.001），其蛋白的表达与甲基化状态呈负关联(rP=-0.625，P<0.001)。结论：子宫内膜腺癌组织中IGFBP？？rP1基因甲基化主要发生在启动子区，且呈低甲基化状态；IGFBP？？rP1启动子区的低甲基化状态可能是IGFBP？？rP1基因在子宫内膜腺癌组织中高表达的调控机制之一。
Aim: To investigate the methylation of insulin like growth factor binding protein？？related protein 1(IGFBP？？rP1) gene and its relationship with the expressions of IGFBP？？rP1 mRNA and protein in endometrial adenocarcinoma tissue. Methods: Methylation？？specific PCR was used to detect the methylation status of IGFBP？？rP1 gene in the promoter region and the first exon region in 45 cases of endometrial adenocarcinoma,30 cases of endometrial atypical hyperplasia, and 30 cases of simple endometrial hyperplasia tissue, and quantitative Real？？time PCR and immunohistochemical SP method were respectively used to detect the mRNA and protein expressions of IGFBP？？rP1.Results: The methylation rate of IGFBP？？rP1 gene in the promoter region was higher than that in the first exon region in the endometrial adenocarcinoma tissue(χ2=6.429，P=0.011). The methylation rate of IGFBP？？rP1 gene in the promoter region of endometrial adenocarcinoma tissue was significantly lower than those in endometrial atypical hyperplasia and simple endometrial hyperplasia tissue(F=14.659,P=0.001). The mRNA and protein expressions of IGFBP？？rP1 gene in endometrial adenocarcinoma tissue were higher than those in endometrial atypical hyperplasia and simple endometrial hyperplasia tissue(F=8.619，χ2=23.611，P<0.05).The expression of IGFBP？？rP1 mRNA in the endometrial adenocarcinoma tissue with the promoter methylation was lower than that without(t=4.758,P=0.001);the expression of IGFBP？？rP1 protein in the endometrial adenocarcinoma tissue with the promoter methylation was negatively associated with the promoter methylation(rP=-0.625，P<0.001).Conclusion: The methylation of IGFBP？？rP1 gene mainly exists in the promoter region of endometrial adenocarcinoma tissue in a low methylation status;the low methylation status in the promoter region of IGFBP？？rP1 may be one of the regulatory mechanisms of the high expression of IGFBP？？rP1 gene in endometrial