甲状腺乳头状癌组织中NIS和RASSF1A基因启动子区CpG岛甲基化状态的研究

Research of CpG island methylation status of NIS and RASSF1A gene promoters in papillary thyroid carcinomas

目的探讨甲状腺乳头状癌及癌旁组织中,甲状腺功能基因钠碘转运体基因(NIS)和甲状腺抑癌基因RAS相关区域家族1A基因(RASSF1A)基因启动子甲基化改变的特点及其相关性。方法采用甲基化特异性PCR方法分别检测NIS和RASSF1A基因启动子的甲基化状况。结果①甲状腺乳头状癌组织中NIS基因启动子甲基化显著高于癌旁组织(P<0.05)。②甲状腺乳头状癌组织中RASSF1A基因启动子甲基化显著高于癌旁组织(P<0.05)。③功能基因NIS启动子甲基化发生显著高于抑癌基因RASSF1A基因启动子的甲基化(P<0.05);功能基因NIS和抑癌基因RASSF1A的启动子的甲基化呈正相关(rs=0.41,P<0.05)。结论 RASSF1A基因和NIS基因启动子异常甲基化是甲状腺乳头状癌发生或发展过程中的分子事件,两者的基因甲基化提示呈一定正相关,可能相互影响共同参与了甲状腺乳头状癌发生、发展过程。

【Objective】 To detect methylation status of the promoter regions of functional gene NIS（sodium iodide symporter,Na＋/I-symporter） and anti-oncogene RASSF1A（RAS association domain Family 1A） in papillary thyroid carcinomas（PTC） and adjacent thyroid tissues（ATT）.【Methods】 Using methylation-specific PCR technique（MSP）,specimens from 34 PTC patients were used to detect methylation of NIS and RASSF1A promoter region.And the results were analyzed by SAS 9.13 software.【Results】 ①The rate of methylation of NIS promoter in PTC was significantly higher than that in ATT（P 0.05）.② The rate of methylation of RASSF1A promoter in PTC was significantly higher than that in ATT（P 0.05）.③The methylation rates of NIS gene was significantly higher than that of anti-oncogene RASSF1A in PTC（P 0.05）.The methylation status of the promoter region of functional gene NIS is in positive correlation with that of anti-oncogene RASSF1A in PTC（rs =0.41,P =0.0158）.【Conclusion】 Methylation of promoter regions in NIS and RASSF1A genes is a common molecular event in human PTC,methylation of these two genes cue some positive correlation and may play some role in the development and progression of PTC.