DNA methylation of MAPK signal-inhibiting genes in papillary thyroid carcinoma

Background: The purpose of this study was to identify the DNA methylation status of the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual-specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and serpin peptidase inhibitor A member 5 (SERPINA5) in thyroid cancer. Materials and Methods: Using 76 papillary thyroid cancer(PTC) tissues and three thyroid cancer cell lines (TPC1, WRO82-1 and XTC), the expression of three genes and DNA methylation were determined by reverse transcription-PCR and methylation-specific PCR. Results: In all cell lines, the expression of DUSP4 and DUSP6 increased; the corresponding gene promoters were unmethylated. However, SERPINA5 gene expression decreased and SERPINA5 DNA was methylated in the TPC1 cell line. With the de-methylating agent 5′-aza-2′-deoxycytidine, SERPINA5 gene expression was restored. In 82.9% of PTC tissues (63/76), the SERPINA5 DNA promoter was methylated, which was associated with a higher v-raf murine sarcoma viral oncogene homolog B1(BRAF) mutation rate in PTC tissues based on multivariate regression (odds ratio=3.573; 95% confidence interval=1.122-11.379; p=0.031). Conclusion: The expression of the MAPK signal-inhibiting gene SERPINA5 decreased in the TPC1 cell line, SERPINA5 expression was regulated by DNA methylation, which was associated with a higher BRAF mutation rate in PTC.