miR-34b基因启动子区甲基化与甲状腺乳头状癌的关系

目的探讨甲状腺乳头状癌（PTC）中微小RNA-34b（miR-34b）基因的表达及其启动子区的甲基化情况,并分析甲基化与其临床病理特征的关系。方法收集2008年9月至2010年10月期间南京医科大学附属淮安第一医院行手术切除的25例PTC患者的癌组织和癌旁组织。采用实时定量PCR法检测其miR-34b mRNA的表达,采用甲基化特异性（MSP）PCR法检测miR-34b基因启动子区的甲基化情况。结果 PTC癌组织中miR-34bmRNA的相对表达量为0.85±0.05,较癌旁组织的1.62±0.09低（P=0.030）。25例PTC癌组织中,有18例（72%）患者的miR-34b基因启动子区发生甲基化,癌旁组织组有10例（40%）,癌组织的甲基化比例较高（P=0.021）。甲基化与PTC患者的年龄、性别、肿瘤大小、TNM分期和包膜浸润均无关（P〉0.05）,而与淋巴结转移有关,发生淋巴结转移者的甲基化比例高于未发生淋巴结转移者（P〈0.05）。结论 PTC癌组织中miR-34b基因启动子区的异常甲基化可能是该基因失活的原因之一,并且可能与PTC的发生、发展以及转移均有关,其机理值得进一步研究。

Relationship Between Methylation of MiR-34b Gene Promoter and Papillary Thyroid Carcinoma

Objective To investigate the expression level and methylation level of micro RNA-34b（miR-34b） gene in papillary thyroid carcinoma（PTC）,and to analyze the relationship between methylation and clinicopathological characters of PTC.Methods PTC tissues and tumor adjacent tissues were collected from 25 patients with PTC who underwent operation in Huai’an First People’s Hospital of Nanjing Medical University from Sep.2008 to Oct.2010.Expression of miR-34b gene and level of methylation in gene promoter were detected by real time PCR and methylationspecific PCR in the 2 kinds of tissues,respectively.Results The expression value of miR-34b mRNA in PTC tissues was 0.85±0.05,which was significantly lower than those of tumor adjacent tissues（1.62±0.09）,P=0.030.There were methylation in 18（72%,18/25）PTC tissues,and 10（40%,10/25）in tumor adjacent tissues,and the ratio of methylation was higher in PTC tissues（P=0.021）.In PTC tissues,methylation was not related to age,gender,tumor size,TNM stage,and invasion of the capsule（P〈0.05）,but was related to lymph node metastasis（P〈0.05）.Ratio of methylation in patients with lymph node metastasis was significantly higher than those of patients with no lymph node metastasis.Conclusion Methylation of miR-34b gene promoter is one of the reasons for inactivation of PTC,and it may be related to the development and metastasis of PTC,which needs to be further investigated.