宫颈癌组织白介素10和干扰素γ基因表达及其启动子区甲基化状态研究

Expressions of IL-10 and IFN-γ Genes and Their Methylation in Promoter Region in Cervical Tissues

目的探讨宫颈癌组织白介素10(IL-10)和干扰素γ(IFN-γ)基因表达及其启动子区甲基化状态。方法选取2011年3月—2012年5月在唐山市工人医院住院部就诊的宫颈癌患者43例为宫颈癌组、宫颈上皮内瘤变(CIN)患者62例为CIN组,另选取同期行全子宫切除的子宫肌瘤患者43例为对照组。采用亚硫酸氢盐测序法(BSP)、甲基化特异性PCR(MSP)和实时荧光定量PCR(RT-PCR)检测三组患者宫颈组织中IL-10和IFN-γ基因的启动子甲基化状态和mRNA表达。结果三组IL-10和IFN-γmRNA水平比较,差异均有统计学意义(P<0.05),其中宫颈癌组和CIN组IL-10 mRNA水平均高于对照组,IFN-γmRNA水平均低于对照组(P<0.01)。三组IL-10基因启动子区-110、-185位点甲基化率比较,差异均有统计学意义(P<0.05),其中宫颈癌组和CIN组IL-10基因启动子区-110位点甲基化率均高于对照组,宫颈癌组IL-10基因启动子区-185位点甲基化率低于对照组(P<0.05)。宫颈癌组IFN-γ基因启动子甲基化率高于CIN组,CIN组高于对照组(P<0.05)。结论 IL-10和IFN-γ基因启动子区甲基化状态影响其在宫颈组织中的表达,宫颈癌患者处于Th2极化状态,可能与宫颈癌的发生有关。

Objective To evaluate the expressions of interleukin-10（IL-10）and gamma-interferon（IFN-γ） and their methylation in promoter region in cervical tissues. Methods Using bisulfite sequencing PCR（ BSP）,methylation-specific PCR（MSP）and real time（RT-PCR）to determine the promoter methylation of IL-10,IFN-γand mRNA expres-sions in cervical tissues in 43 uterine cervix cancer patients（ UCC group）,62 cervical intraepithelial neoplasia patients（ CIN group）,43 hysteromyoma patients（control group）who visited Tangshan Labor Hospital from March 2011 to May 2012. Re-sUlts There was significant difference in IL-10,IFN-γ mRNA levels among the 3 groups（P〈0. 05）,and IL-10 mRNA higher,IFN-γmRNA lower in groups UCC,CIN than in control group（P〈0. 01）. There was difference in methylation rate of IL-10 gene promoter-110,-185 locus among the 3 groups（P〈0. 05）,and that of promoter-110 locus higher,that of promoter-185 locus lower in groups UCC,CIN than in control group（P〈0. 05）. Methylation rate of IFN-γ gene promoter was higher in UCC group than in CIN group,higher in CIN group than in control group（P〈0. 05）. ConclUsion Methylation in promoter region influences the expressions of IL-10,IFN-γgenes in cervical tissues. Th2 polarization of UCC patients may be related to occurrence of UCC.