促进甲状腺激素受体和 p16 抑癌基因甲基化与乳头状甲状腺癌临床病理的关系

doi:10.3969/j.issn.1006-7795.2012.03.016

首都医科大学学报 ›› 2012, Vol. 33 ›› Issue (3): 361-365.doi: 10.3969/j.issn.1006-7795.2012.03.016

促进甲状腺激素受体和 p16 抑癌基因甲基化与乳头状甲状腺癌临床病理的关系

戴亚丽, 蔡德鸿, 陈宏, 张桦, 张震, 李静

南方医科大学珠江医院内分泌科, 广州 510282

收稿日期:2012-01-10 修回日期:1900-01-01 出版日期:2012-06-21 发布日期:2012-06-21
通讯作者: 蔡德鸿

The relevance between the promoter hypermethylation of tshr and p16 gene and clinicopathological parameters in human papillary thyroid carcinoma

DAI Ya-li, CAI De-hong, CHEN Hong, ZHANG Hua, ZHANG Zhen, LI Jing

Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

Received:2012-01-10 Revised:1900-01-01 Online:2012-06-21 Published:2012-06-21

摘要/Abstract

摘要： 目的通过对乳头状甲状腺癌(papillary thyroid carcinoma,PTC)两种抑癌基因:促甲状腺激素受体(thyroid stimulating hormone receptor,tshr)和 p16 启动子甲基化的研究,分析其启动子甲基化与患者临床病理参数之间的关系,寻找PTC的发生机制,并探讨2个抑癌基因在PTC的发生中有无关联性。方法提取50例PTC组织和32例对照组织DNA,进行甲基化修饰,采用甲基化特异性PCR(methylation-specific PCR,MSP)检测两种抑癌基因启动子区甲基化的情况;用测序方法证实甲基化的存在;采用SPSS13.0软件分析两种抑癌基因甲基化之间的关联性及两种抑癌基因启动子甲基化和主要的临床病理参数的关系。结果50例PTC中,有34例(68%)tshr基因、27例(54%)的 p16 基因启动子发生了甲基化;32例对照组中,2个抑癌基因的甲基化分别为7例(21.9%)和5例(15.6%), PTC组2个抑癌基因启动子甲基化率均显著高于对照组,差异有统计学意义(χ²值分别为16.61和12.08,P<0.05);2个抑癌基因相关性分析,tshr和 p16 之间不存在关联性(r=0.23,P>0.05);两种基因启动子在有淋巴结转移的PTC的甲基化率高于无淋巴结转移的病例(χ²值分别为5.82和5.10,P<0.05)。结论两种抑癌基因启动子甲基化与PTC的发生有关,两种基因启动子甲基化在PTC的发生中可能没有相关性,但在恶性进展中可能发挥一定作用。

关键词: 乳头状甲状腺癌, 抑癌基因, 甲基化, 临床病理, 相关性

Abstract: Objective To study the expression of the tumor suppressor gene thyroid stimulating hormone receptor (tshr) and p16 in papillary thyroid carcinoma(PTC),analyse of the relationship between two promoter methylation and clinicopathological parameters,and to explore the correlation between the occurrence of tumor and the aberrant promoter methylation of two tumor suppressor genes. MethodsThe promoter methylation status of two tumor suppressor gene in 50 cases of PTC and 32 cases of controls were examined by using methylation-specific PCR technique (MSP). Using gene sequencing to test if the hypermethylation existed in promoter of two tumor suppressor genes. The relationship of two tumor suppressor genes promoter methylation and the correlation between their methylation and the main clinical pathologic parameters was analyzed by SPSS 13.0 software. Results Hypermethylation was detected in 68.0% (34/50) tshr gene and 54.0%(27/50) p16 gene in PTC in promoter region while hypermethylation was detected in 21.9%(7/32)tshr gene and 15.6%(5/32) p16 gene in control in promoter region.The rate of promoter methylation in PTC was significantly higher than that in control (the χ² was 16.61 and 12.08 separately,P<0.05). The sequencing confirmed that there were the CG →TG transmission in promoter of two tumor suppressor genes.The correlation analysis showed that there was no association between tshr and p16 gene hypermethylation(r=0.23,P>0.05);The rate of tshr and p16 gene methylation was higher in PTC with lymph node metastasis than that without lymph node metastasis(the χ² was 5.82 and 5.10 separately,P<0.05). Conclusion Methylation of two tumor suppressor genes in promoter region is a common molecular event and may be involved in the genesis and development of human PTC.tshr and p16 gene promoter methylation may play a role in malignant progression of PTC.

Key words: papillary thyroid carcinoma, tumor suppressor gene, methylation, clinicopathological, relevance

中图分类号:

R 739.91

戴亚丽;蔡德鸿;陈宏;张桦;张震;李静. 促进甲状腺激素受体和 p16 抑癌基因甲基化与乳头状甲状腺癌临床病理的关系[J]. 首都医科大学学报, 2012, 33(3): 361-365.

DAI Ya-li;CAI De-hong;CHEN Hong;ZHANG Hua;ZHANG Zhen;LI Jing. The relevance between the promoter hypermethylation of tshr and p16 gene and clinicopathological parameters in human papillary thyroid carcinoma[J]. Journal of Capital Medical University, 2012, 33(3): 361-365.

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促进甲状腺激素受体和 p16 抑癌基因甲基化与乳头状甲状腺癌临床病理的关系

The relevance between the promoter hypermethylation of tshr and p16 gene and clinicopathological parameters in human papillary thyroid carcinoma

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