Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
The Colorectal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
Aging (Albany NY). 2023 Oct 6;15(19):10607-10626. doi: 10.18632/aging.205100.
To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC).
TTK expression in PTC and normal groups were compared using TCGA data and 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 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.
TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis ( < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all < 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 ( < 0.05). Moreover, miR-582-5p was an upstream target of TTK.
TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.
探讨苏氨酸酪氨酸激酶（TTK）在甲状腺乳头状癌（PTC）中的作用及临床意义。
利用 TCGA 数据和实验比较 PTC 组和正常组中 TTK 的表达情况。评估 TTK 的预后价值及其在 PTC 去分化中的可能作用。然后通过实验分析 TTK 参与 PTC 的发生和进展。接下来，进行富集和免疫细胞浸润分析，以揭示可能的机制。最后，预测了靶 miRNAs，然后进行了荧光素酶报告实验。
PTC 中 TTK 上调，其高表达水平与不良预后显著相关（<0.05）。有趣的是，TTK 与甲状腺分化评分（TDS）呈负相关，TDS 较高的患者生存时间更长（均<0.05）。TTK 敲低抑制 PTC 细胞的生长、迁移和侵袭。此外，TTK 参与代谢过程并调节细胞黏附分子途径。其过表达与免疫细胞浸润呈正相关（<0.05）。此外，miR-582-5p 是 TTK 的上游靶标。
TTK 可作为 PTC 发生和预后的潜在生物标志物，尤其是对可能分化为侵袭性更强的甲状腺癌的患者。
