Analysis of promoter methylation of CYP1A1 and CYP1B1 gene in thyroid cancer / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the promoter methylation of drug metabolism genes CYP1A1 and CYP1B1 in thyroid cancer and its relationship with clinical pathological characteristics. Method 201 cases of thyroid cancer and 23 cases of normal thyroid tissues were involved. Methylation-specific PCR ( MSP ) was performed to analyze promoter methylation of CYP1A1 and CYP1B1 genes in the above tissues to detect the frequency of methylation positive, compare the promoter methylation level of CYP1A1 and CYP1B1 genes in papillary thyroid carcinomas ( PTC) and the controls. Five thyroid cancer cell lines were treated with methyltransferase inhibitor 5-Aza-dC for 5 days, and real time PCR ( RT-PCR) was performed to evaluate the mRNA expression of CYP1A1 and CYP1B1 genes. Logistic regression was used to analyze the correlation between the aberrant methylation and the clinical features. Results Aberrant methylation status in promoter region of CYP1A1 and CYP1B1 genes were detected in all kinds of thyroid cancers. Compared with control tissues, the methylation in promoter regions of CYP1A1 in PTCs was significantly higher, while that in promoter regions of CYP1B1 was lower (P<0.05). In vitro, 5-Aza-dC treatment significantly increased the CYP1A1 gene mRNA expression for 6. 92 and 8. 30 times in K1 and C643 cell lines respectively and restored CYP1B1 gene mRNA expression for 7.62 times in K1 cell line. Compared with the controls, PTCs with methylation in promoter regions of CYP1B1 had decreased lymphatic metastasis rate. Conclusion The methylation in promoter regions of CYP1A1 and CYP1B1 gene may regulate their mRNA expressions. Aberrant methylation of the promoter region of CYP1B1 is associated with lymph node metastasis in PTC.