APC基因甲基化与其表达在子宫颈癌及癌前病变中的相关性研究

Promoter methylation of APC gene in cervical cancer and precancerous lesions and its association with APC expression

目的探讨子宫颈癌及癌前病变中APC基因的甲基化与其表达的相关性。方法将手术切除的92例子宫颈或子宫体疾病患者的子宫颈组织分为3组,其中子宫颈鳞状细胞癌Ⅰb1期33例,CINⅢ28例,子宫颈正常者31例(对照组)。行甲基化特异性PCR实验,检测3组子宫颈组织中腺瘤性结肠息肉病(adenomatous polyposis coli,APC)基因的甲基化情况;行RT-PCR,检测各组织中APC基因mRNA水平的表达情况;应用免疫组织化学(S-P法)检测APC蛋白在各组织中的表达情况。结果子宫颈癌组中APC基因的mRNA表达率为30.3%(10/33)、APC蛋白表达率36.4%(12/33)及甲基化率63.6%(21/33);与CINⅢ组[46.4%(13/28)、32.1%(9/28)、57.1%(16/28)]比较,差异均无统计学意义(P>0.05),而与对照组[61.3%(19/31)、67.7%(21/31)、22.6%(7/31)]比较,差异具有统计学意义(P<0.05)。子宫颈癌及CINⅢ组织中APC基因甲基化水平与APC蛋白和mRNA的表达均呈负相关(均P<0.05)。结论 APC基因的甲基化和低表达可能与子宫颈癌的发生、发展密切相关。

Objective To investigate the methylation status of APC gene in cervical cancer and precancerous lesions and its association with APC gene expression. Methods Ninety-two cervical tissue samples were collected, including 33 cases of cervical squamous cell carcinoma stage I bl, 28 cases of CIN Ⅲ and 31 cases of normal cervical tissues. DNA methylation status of APC gene in cervical tissues was detected by methylation-specific PCR. The expression of APC mRNA was detected by reverse transcription-PCR （RT-PCR） and the expression of APC protein was detected by immunohistochemistry S-P methods. Results The expression rates of APC mRNA and protein, methylation status of APC gene in cervical carcinoma were 30.3% （ 10/33 ）, 36.4% （ 12/33 ） and 63.6% （21/33） ,which were significantly different from those in normal cervical tissues [ 61.3% （ 19/31 ）, 67.7% （ 21/31 ） and 22.6% （ 7/31 ）, P 〈 0.05 ], but not from those in CIN Ⅲ tissues [46.4% （13/28）, 32.1% （9/28） and 57.1% （16/28） ,P 〉0.05 ]. APC gene methylation status in cervical carcinoma and CIN m tissues was negatively correlated with APC protein and mRNA expressions （ all P 〈 0.05 ）. Conclusion APC methylation and the low levels of APC protein and mRNA may be associated with the development and progression of cervical cancer.