Methylation Degrees of NIS and TIMP-3 Promoters in Well-Differentiated Thyroid Tumors

Abstract

Background The aim of this study was to investigate the DNA methylation pattern in CpG islands of NIS and TIMP-3 promoters in thyroid cancers and the matched non-tumoral tissues as well as multinodular goiter (MNG) tissues. This cross-sectional study was performed on total 64 patients including 28 papillary thyroid cancer (PTC), 9 follicular thyroid cancer (FTC) and 27 MNG cases. Method: The bisulfite sequencing PCR technique was used to evaluate the promoter methylation pattern of the NIS and TIMP-3 genes. Results NIS mRNA levels were decreased in both of PTC and FTC tumoral tissues compared to their adjacent normal tissues (P = 0.04 and P = 0.03, respectively). TIMP-3 expression was also reduced in both PTC and FTC tumoral tissues compared to the adjacent non-tumoral tissues (P = 0.02 and P = 0.03, respectively). Moreover, a significant reduction in TIMP-3 expression was observed in FTC tissues compared to the MNG samples (P = 0.05). The methylation on NIS promoter was not a common event in PTC samples, but it was frequent in FTC (P < 0.05). A significant hyper-methylation was shown in TIMP-3 promoter in both PTC and FTC tissues compared to the non-tumoral and MNG samples (P < 0.05). Conclusion Aberrant promoter DNA methylation suggests potential utility to differentiate benign and malignant PTC and FTC tissues for early diagnosis, and contribution for personalized clinical management and surveillance. According to the reversibility of DNA methylation, these events may be potential targets for demethylating treatments.