人口腔白斑和口腔鳞癌组织中RASSF1和RASSF2的甲基化分析研究

Methylation changes of RASSF1 and RASSF2 in oral leukoplakia and oral squamous cell carcinoma

目的探讨口腔白斑(OLK)、口腔鳞状细胞癌(OSCC)与正常口腔黏膜组织中抑癌基因RASSF1、RASSF2的甲基化状态变化与病理学及人口学资料的关系。方法收集就诊于首都医科大学附属北京口腔医院黏膜科OLK 87例,OSCC 39例,30例正常口腔黏膜作为对照,采用内切酶消化法和实时定量PCR的方法对RASSF1和RASSF2甲基化状态进行研究。结果在正常口腔黏膜中,RASSF1、RASSF2启动子区处于未甲基化状态,口腔白斑中RASSF1甲基化阳性率为44. 83%,RASSF2甲基化阳性率为52. 87%,与正常对照相比显著增高(P <0. 017);口腔鳞癌RASSF1甲基化阳性率为25. 64%,RASSF2甲基化阳性率为43. 59%,与正常对照相比显著增高(P <0. 017)。结论抑癌基因RASSF1、RASSF2启动子甲基化有成为口腔黏膜癌变早期标志物的可能性。

Objective To investigate the relationship of the promoter methylation of tumor suppressor genes RASSF1 and RASSF2 with the gender,age,site,smoking and pathology in oral leukoplakia and oral squamous cell carcinoma patients.Methods The promoter methylation status of RASSF1 and RASSF2 in 87 oral leukoplakia (OLK)and 39 oral squamous cell carcinoma (OSCC)patients tissues was analyzed using methylation dependent enzyme digestion and quantitative PCR.Results In 30 normal oral mucosa controls,no promoter methylation of RASSF1 and RASSF2 was found. In OLK tissues,hypermethylation rates of RASSF1 and RASSF2 were 44.83% and 52.87%,respectively.Methylation rates of RASSF1and RASSF2in the OLK cases were significantly higher than those in the normal controls (P<0.017).In OSCC patients,hypermethylation rate of RASSF1 was 25.64%,and of RASSF2 was 43.59%.The Methylation rates of RASSF1 and RASSF2 in the OSCC cases were higher than those in the normal controls (P<0.017).Conclusion Promoter methylation of RASSF1 and RASSF2 is more frequent in oral precancerous lesion and OSCC patients,which may have potential to be biomarkers of oral carcinogenesis.