M6A Demethylase FTO Plays a Tumor Suppressor Role in Thyroid Cancer.

ABSTRACT

The purpose of this study was to investigate the expression and clinical significance of N6-methyladenosine demethylase FTO in thyroid cancer. Bioinformatic analysis showed that FTO expression was downregulated in thyroid cancer tissues and correlated with lymph node metastasis in thyroid cancer patients. We conducted experimental verification by collecting Asian samples. The results of quantitative reverse transcription-PCR showed that the mRNA expression of FTO in the blood of 30 thyroid cancer patients was lower than that of the control population. At the same time, we found that FTO expression was negative in tissues of 16/56 (28.57%) thyroid cancer cases and 4/40 (10.00%) nontumor thyroid cases through the immunohistochemical method, indicating a lower FTO expression in thyroid cancer tissues than nontumor thyroid tissues (p < 0.05). In addition, the protein expression of FTO was significantly related to the tumor grade and lymph node metastasis in thyroid cancer patients (p < 0.05), but not to other clinicopathological features. Multivariate logistic regression analysis showed that FTO expression was an independent risk factor for tumor grade. Survival analysis showed no significant difference in the disease-free survival time of thyroid cancer patients between high expression and low expression groups of FTO. Furthermore, bioinformatic analysis found that promoter DNA methylation and copy number variation might cause downregulated FTO and then affect TP53 pathways in thyroid cancer. We found that FTO expression was downregulated in thyroid cancer tissues and related to the progression of thyroid cancer, suggesting a tumor suppressor role of FTO in thyroid cancer.