Research Paper Volume 15, Issue 19 pp 10607—10626

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

Jun-Jie Ma1, , Cheng Xiang1, , Jian-Wei Wang2, ,

  • 1 Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China
  • 2 The Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China

Received: May 12, 2023       Accepted: September 9, 2023       Published: October 6, 2023
How to Cite

Copyright: © 2023 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


TTK: threonine tyrosine kinase; PTC: papillary thyroid cancer; TDS: thyroid differentiation score; THCA: thyroid cancer; SAC: spindle assembly checkpoint; GSEA: gene set enrichment analysis; ROC: receiver operating characteristic; DFI: disease-free interval; DSS: disease-specific survival; OS: overall survival; PFI: progression-free interval; DEGs: differentially expressed genes; EMT: epithelial-mesenchymal transition.