Methylation analysis of drug metabolism and transport genes in papillary thyroid cancer

The genes encoding drug-metabolizing enzymes and transporters play an important role in maintaining the normal life processes of human body. Their disorder or defect will lead to the occurrence and development of various 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 investigate promoter 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 data showed 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 tissues compared with PTC, particularly ABCB1, ABCB4, CYP1B1 and CYP24A1 (P < 0.05). Conversely, CYP1A1, CYP27B1, SLC19A3, and SLC26A2 were more frequently methylated in PTC. Moreover, promoter methylation of several genes was closely associated with certain clinicopathologic features, such as tumor stage, extrathyroidal invasion, and lymph node metastasis. Of note, demethylation agant 5-Aza-2'-dC could induce the expression of most of methylated genes in thyroid cancer cell lines. Thus, our data first revealed a distinct methylation profiling in drug metabolism and transport genes between PTC and normal thyroid tissues, strongly suggesting that these epigenetic events may play a critical role in thyroid tumorigenesis.