PAX9、SLC5A8、CDH13 And ZBED3 Methylation In Thyroid Cancer

Objective:To screen genes specifically hypermethylated in thyroid cancer and detect methylation status of PAX9、SLC5A8、CDH13 and ZBED3 in malignant and benign thyroid lesions, and to discuss the meaning of gene methylation status in carcinogenesis of thyroid cancer, diagnosis and prognosis. Methods:Using MSP technique to screen genes in thyroid cancer and identify genes specifically hypermethylated in thyroid cancer. Detecting methylation status of PAX9、SLC5A8、CDH13 and ZBED3 in thyroid cancer, adjacent normal tissue, benign thyroid lesion and normal thyroid tissue, and analyzing the diagnostic and prognostic effects of gene methylation with clinic and pathologic features. Results:The methylation rate of PAX9, SLC5A8, CDH13 and ZBED3 in thyroid cancer was 33%,28%,32% and 17% respectively, and the methylation rate in adjacent normal tissue was 33%,37%,30% and 17% respectively. There was no statistic difference between thyroid cancer and adjacent normal tissue in methylation status of PAX9、SLC5A8、CDH13 and ZBED3. The methylation rate of PAX9, SLC5A8, CDH13 and ZBED3 in benign thyroid lesions was 38%,43%,14% and 57% respectively, and the methylation rate in matched normal tissue was 13%, 14%,29% and 14%. The methylation rate of PAX9, SLC5A8 and ZEBD3 was higher in benign thyroid lesion, compared with adjacent normal tissue. When the methylation status of PAX9、SLC5A8、CDH13 and ZBED3 was independently analyzed, the incidence rate of bilateral lesions and cervical lymph node metastasis was 35% and 76% in thyroid cancer group with SLC5A8 hypermethylation, which was statistically higher than the incidence rate in SLC5A8 hypomethylation subgroup (15% and 52% respectively). The average diameter of thyroid cancer lesion in ZBED3 hypermethylation subgroup was 19.5mm, longer than that in ZBED3 hypomethylation subgroup (14.2mm). Other genes were not statistically related with age, lesion site, lesion number, lesion size and cervical lymph node metastasis. When the methylation status of PAX9、SLC5A8. CDH13 and ZBED3 were jointly analyzed, in thyroid cancer group with hypermethylation detected for at least once in four genes (M1), the incidence of bilateral lesions, diameter≥15mm, VI lymph node metastasis and cervical lymph node metastasis was 33%,50%, 69% and 74% respectively, which were statistically higher than the incidences in thyroid cancer group with no hypermethylation in all four genes (MO). Conclusion:Hypermethylation of PAX9、SLC5A8、CDH13 and ZBED3 is presented in thyroid cancer, adjacent normal tissue of thyroid cancer and benign thyroid lesions, but no methylation difference is found between thyroid cancer and its adjacent normal tissue. Jointed methylation status of PAX9、SLC5A8、CDH13 and ZBED3 is statistically related with lesion site, size, VI lymph node metastasis and cervical lymph node metastasis, which helps predicting the status of primary thyroid cancer and lymph node metastasis and benefits staging, adopting optimal surgical pattern and prognosis.