TSLC1基因异常甲基化及与HPV的关系在宫颈癌发生发展中的意义

目的:探讨TSLC1基因启动子甲基化状态以及与HPV感染的关系在子宫颈癌发生发展中的意义。方法:用甲基化特异性聚合酶链反应(MSP)法检测68例原发性宫颈癌,67例CIN及29例慢性宫颈炎症石蜡包埋组织中TSLC1基因甲基化状态。用聚合酶链反应(PCR)法检测人乳头瘤病毒(HPV)DNA的感染状况。结果:宫颈癌组织中45例异常甲基化(66.2%),其中鳞癌67.8%(40/59),腺癌55.5%(5/9);67例宫颈上皮内瘤变组织中29例可见异常甲基化(43.3%);29例慢性炎症组织中2例甲基化(6.9%);将鳞癌、腺癌、CIN与慢性炎症比较,鳞癌与CIN比较,CINⅡ～Ⅲ与CINⅠ比较均显示差异有统计学意义(P<0.05),腺癌与CIN比较,鳞癌分化程度之间的差异无统计学意义(P>0.05)。HPV感染率宫颈癌组51.5%(35/68),CINⅠ23.1%(6/26),CINⅡ～Ⅲ41.5%(17/41),慢性炎症组17.2%(5/29);TSLC1甲基化与HPV感染相关性比较,CIN组之间差异有统计学意义(P<0.05),宫颈癌组之间的差异则无统计学意义(P>0.05)。结论:TSLE1基因启动子区CPG岛的高甲基化是导致TSLC1基因失活的重要机制,可能参与宫颈癌的发生;它与HPV之间的关系提示TSLC1基因可能是宫颈细胞癌变过程中的早期事件。

Hypermethylation of TSLC1 promoter and its relationship with HPV infection in human cervix carcinoma pathogenesis

Objective:To determine the methylation status in TSLC1 tumor suppressor gene promoter,and its relationship with HPVs infection in the pathogenesis of human cervica1 carcinoma.Methods:Methylation-specific PCR(MSP)assays were used to analyze the methylation of 5'-CpG island in promoter of TSLC1 gene in 68 cervica1 carcinoma,67 dysplasia and 29 cervicitis tissues.HPV infection was detected by polymerase chain reaction(PCR)for HPV DNA.Results:Hypermethylation of TSLC1 was observed in 66.2%(45/68)cervical cancers67.8%(40/59)squamous cancers and 55.5%(5/9)adenocarcinomas,respectively];43.3%(29/67)cervical intraepithelial neoplasia(CIN),and 6.9%(2/29)cervicitis tissues.Compared to cervicitis group,all of squamous cancer,adenocarcinoma and CIN groups exhibited significant differences(P<0.05).Significant differences have also been detected between squamous cancer and CIN groups,and between stageⅠ and Ⅱ~Ⅲ of CIN groups.In contrast,statistical difference(P>0.05)were not detected between adenocarcinoma and CIN,or between adenocarcinoma and different stages of CIN.HPV infection was found in 51.5%(35/68)cervica1 carcinomas,23.1%(6/26)CINⅠ,41.5%(17/41)CINⅡ~Ⅲ,and 17.2%(5/29)cervicitis.Statistical analysis for the association of hypermethylation of TSLC1 and HPV infection revealed that:the significant differences(P<0.05)were observed in the methylated tissues of CIN group,but not in the group of cervical carcinoma(P>0.05).Conclusion:Methylation of 5'-CpG island in TSLC1 gene is associated with HPV infection in cervical carcinoma and CINⅡ~Ⅲ tissues,which may be underlying the mechanism of TSLC1 gene inactivation in the pathogenesis of human cervical carcinoma.