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[摘要] 目的 本研究分析甲状腺乳头状癌中促甲状腺素受体与钠碘转运体基因启动子区甲基化状况，探讨甲状腺功能基因甲基化与甲状腺乳头状癌病理侵袭性之间相关性。 方法 采用甲基化荧光实时特异聚合酶链反应甲状腺乳头状癌中TSHR与NIS基因启动区异常甲基化情况，探讨该区甲基化与病理参数之间的关系，以及两基因甲基化之间相关情况。 结果 甲状腺癌中NIS与TSHR基因甲基化均高于癌旁组织，差异有统计学意义（P<0.01）。TSHR启动区域5’-CpG岛甲基化分别与病灶多少、颈淋巴结转移及局部侵犯有关（P<0.05），NIS基因启动子区域5’-CpG岛甲基化分别与患者年龄、多病灶、颈淋巴结转移及病理分期有关（P<0.05），两基因甲基化相关性分析：①TSHR启动子甲基化发生显著高于NIS；②TSHR与NIS基因的启动子区甲基化有关系。 结论 乳头状甲状腺癌的功能基因TSHR与NIS基因启动区甲基化是常见现象，可能在甲状腺癌的发生发展过程中发挥重要作用，可能与肿瘤侵袭性相关。两组基因甲基化具一定相关性，联合两个基因启动子区域甲基化检测可能更有意义。
[关键词] 甲状腺乳头状癌（PTC）；钠/碘协同转运体（NIS）；促甲状腺素受体（TSHR）；甲基化；实时荧光定量甲基化-PCR
[中图分类号] R736.1 [文献标识码] A [文章编号] 1673-9701（2016）21-0001-05
[Abstract] Objective To investigate the methylation status of the promoter region of NIS and TSHR gene promoter region in papillary thyroid carcinomas（PTC），and relation between Methylation of TSHR and NIS gene promoter region correlated and aggressiveness. Methods The promoter region of TSHR and NIS 5"-CpG island methylation of tumor tissue and corresponding adjacent thyroid tissues were detected by real time methylation- specific PCR（qMSP）. The relationship between methylation status and clinical pathological parameters were analyzed. In addition，the correlation between methylation of two genes was studied. Results The rate of methylation of TSHR and NIS were higher than adjacent tissues（P<0.01）.Significant correlation existed among TSHR gene promoter 5"-CpG island methylation with lesions numbers， local invasion， lymph node metastasis respectively（P<0.05），but not with clinical stage， gender and age.Similarly，Significant correlation existed among NIS methylation with patient age，lesions numbers， lymph node metastasis and clinical stage，respectively（P<0.05）， but not with tumor size， local invasion andgender. Relationship between NIS methylation and TSHR methylation in Papillary Thyroid Carcinomas：（1）The methylation rates of TSHR gene was significantly higher than that of NIS in PTC（P<0.01）；（2）The relationship of methylation status of the promoter region of TSHR and NIS in PTC was positive correlation（P<0.01）. Conclusion Methylations of TSHR and NIS gene in promoter region are common molecular events， which make significant role in the development of PTC，may enhance tumor aggressiveness.
[Key words] Papillary thyroid carcinomas（PTC）； Thyroid stimulating hormone receptor（TSHR）； Na+/I- symporter，（NIS）； Methylation； Real time methylation-specific PCR （qMSP）
近年来甲状腺癌显著增高，已成为发病率增长速度最快的实体恶性肿瘤之一[1]。天津市肿瘤医院头颈肿瘤科的调查资料显示，天津等沿海地区是甲状腺癌的高发地区，发病率明显高于内陆地区，且有继续上升趋势，近20年来由0.8/10万上升至2.5/10万。浙江省甲状腺癌报告平均发病率为8.37/10万，死亡率随年龄增加而上升，2007～2011年甲状腺癌发病率每年以接近30%的速度快速上升，已经成为发病率上升最快的肿瘤之一[2]。美国国立癌症研究院2010年发布数据表明全美的甲状腺癌年发病数已经超过40 000例，累积患病数超过400 000例[3]。