TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer

Objective: To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC). Methods: TTK expression in PTC and normal groups were compared using TCGA data and in vitro experiments. The prognostic value of TTK and its possible role in PTC dedifferentiation was evaluated. Next, TTK involvement in PTC occurrence and progression was analyzed via in vitro experiments. Subsequently, analyses of enrichment and immune cell infiltration were conducted to reveal the possible mechanism. Finally, we predicted the target miRNAs followed by performing a luciferase reporter experiment. Results: TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis (P < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all P < 0.05). PTC cell growth, migration, and invasion were inhibited upon TTK knockdown. Besides, TTK was involved in metabolic processes and regulated cell adhesion molecules pathway. Its overexpression was positively associated with immune cell infiltrates (P < 0.05). Moreover, miR-582-5p was an upstream target of TTK. Conclusion: TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.