Methylation Analysis of Drug Metabolism and Transport Genes in Papillary Thyroid Cancer
Methylation Analysis of Drug Metabolism and Transport Genes in Papillary Thyroid Cancer
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甲状腺乳头状癌药物代谢和转运基因的甲基化分析
DOI：
10.1166/asl.2012.4245
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Bingyin Shi
中科院分区：
文献类型：
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作者：
Lihong Zhang;侯鹏;Jing Shi;Meiju Ji;Wei Liu;Na Wang;Haixia Guan;Li Xu;Nongyue He;Bingyin Shi
编码药物代谢酶和转运体的基因在维持人体正常生命过程中起着重要作用。它们的紊乱或缺陷会导致各种疾病的发生和发展。除了遗传改变外，表观遗传异常，如启动子甲基化，在包括甲状腺癌在内的早期疾病中起着关键作用。本研究的目的是利用甲基化特异性PCR（MSP）研究一组药物代谢和转运基因的启动子甲基化，并探讨它们与乳头状甲状腺癌（PTC）临床病理特征的关系。我们的数据显示，这些基因在PTC和正常甲状腺组织中异常甲基化。与PTC相比，ABCB1、ABCB4、ABCG2、CYP1B1、CYP24A1、CYP39A1和SLC1A2在正常甲状腺组织中甲基化频率更高，尤其是ABCB1、ABCB4、CYP1B1和CYP24A1 (P CYP1A、CYP27B1、SLC19A3和SLC26A2在PTC中甲基化频率更高。此外，一些基因的启动子甲基化与某些临床病理特征密切相关，如肿瘤分期、甲状腺外侵袭和淋巴结转移。值得注意的是，去甲基化剂5-Aza-2 ' -dC可以诱导甲状腺癌细胞中大多数甲基化基因的表达。因此，我们的数据首次揭示了PTC和正常甲状腺组织之间药物代谢和转运基因的独特甲基化谱，强烈表明这些表观遗传事件可能在甲状腺肿瘤发生中发挥关键作用。
The genes encoding drug-metabolizing enzymes and transporters play an important role in maintaining thenormal life processes of human body. Their disorder or defect will lead to the occurrence and development ofvarious diseases. In addition to genetic alterations, the abnormalities of epigenetic, such as promoter methylation,play a key role in the early disease, including thyroid cancer. The aim of present study was to investigatepromoter methylation of a panel of drug metabolism and transport genes using methylation-specific PCR(MSP) and explore their association with clinicopathologic features in papillary thyroid cancer (PTC). Our datashowed that these genes were aberrantly methylated in PTC and normal thyroid tissues. ABCB1, ABCB4, ABCG2, CYP1B1, CYP24A1, CYP39A1 and SLC1A2 were more frequently methylated in normal thyroid tissuescompared with PTC, particularly ABCB1, ABCB4, CYP1B1 and CYP24A1 (P CYP1A, CYP27B1, SLC19A3, and SLC26A2 were more frequently methylated in PTC. Moreover, promoter methylationof several genes was closely associated with certain clinicopathologic features, such as tumor stage, extrathyroidalinvasion, and lymph node metastasis. Of note, demethylation agant 5-Aza-2′-dC could induce theexpression of most of methylated genes in thyroid cancer cell lines. Thus, our data first revealed a distinctmethylation profiling in drug metabolism and transport genes between PTC and normal thyroid tissues, stronglysuggesting that these epigenetic events may play a critical role in thyroid tumorigenesis.