Abstract:Objective To explore the roles of 20 m6A methylation regulators in the occurrence, development, and prognosis of papillary thyroid cancer (PTC).Methods Data of 395 PTC patients, including para-carcinoma tissue in 59 cases, were obtained from the TCGA dataset. The differentiated expressions of the 20 m6A regulators were compared, and their correlations to the clinical data of PTC (gender, T stage, cervical lymph node metastasis, etc.) were analyzed. The prognostic-related m6A regulators were identified, and the predictive model for prognosis of PTC was established using the least absolute shrinkage and selection operator (LASSO) regression. In addition, the relationships between the prognostic-related m6A regulators and the immune cells were further explored. All the statistical analysis work was performed by the R foundation.Results A total of 15 m6A-regulated genes were up-regulated in PTC, and 3 genes were down-regulated. HNRNPC and IGF2BP2 were positively and ALKBH5 was negatively correlated to the lymph node metastasis of PTC. HNRNPC and IGF2BP2 were correlated to the T stage. YTHDF1 was correlated to gender. METTL14, YTHDC1, YTHDF2, and HNRNPA2B1 were correlated to the clinical stage of PTC. High expressions of FTO, IGF2BP1 and YTHDF3 resulted in poor prognosis. The established prognostic model revealed that the areas under the ROC curve of three-year and five-year survival rates were 0.753 (95%CI 0.615-0.891) and 0.729 (95%CI 0.613-0.846). YTHDF3 was correlated to the infiltrations of endothelial cell, macrophage cell, NK cell and T cell CD4+, while FTO was correlated to the infiltrations of macrophage cell, NK cell, T cell CD4+ and T cell CD8+.Conclusion The m6A regulators play important roles in the occurrence and development of PTC, and may be severed as potential biomarkers for PTC treatment.
