Wang Zhe-Xiang, Ren Shao-Chun, Ren Jing
The School of Medical Laboratory, Tianjin Medical University, Tianjin, China.
Stomatology, Tianjin Medical University, Tianjin, China.
Arch Med Sci. 2021 Jan 25;18(3):775-785. doi: 10.5114/aoms/115135. eCollection 2022.
Osteosarcoma (OS) is the most common primary bone tumor, and the main affected population is adolescents. The survival of OS patients was 10-20% when surgery was used as a single treatment. There is less basic research on OS than other tumors, and we need more ways to improve the survival rate. Phosphotyrosine picked threonine kinase (TTK) has been widely reported as an oncogene in multiple types of cancers, and it is also known as a clinical therapeutic target. This study aims to assess TTK expression levels in human OS tissues and its link with the clinical characteristics of OS patients, and to evaluate the potential role in OS development.
Immunohistochemical (IHC) assays were conducted to detect the expression levels of TTK in a total of 74 OS tissues and the corresponding adjacent tissues. Furthermore, according to the staining intensity of TTK in tumor tissues, patients were divided into TTK high and low expression groups. The possible correlation between TTK expression levels and clinical features were analyzed, and the effects of TTK on OS cell proliferation were detected through colony formation and cell counting kit-8 (CCK8) assays. The effects of TTK on tumor growth were detected using an animal model.
Phosphotyrosine picked threonine kinase was abnormally highly expressed in human OS tissues. Meanwhile, TTK was significantly correlated with the clinical characteristics such as tumor size ( = 0.004*) and clinical stage ( = 0.014*) of OS patients. Our results also revealed that the inhibition of TTK dramatically suppressed the proliferation of OS cells and blocked tumor growth in mice.
We demonstrated the involvement of TTK in the development of OS, and therefore we suggest that TTK should be considered as a promising therapy target for OS.
骨肉瘤（OS）是最常见的原发性骨肿瘤，主要患病人群为青少年。单纯采用手术治疗时，骨肉瘤患者的生存率为10%-20%。与其他肿瘤相比，关于骨肉瘤的基础研究较少，我们需要更多方法来提高其生存率。磷酸酪氨酸特异性苏氨酸激酶（TTK）在多种癌症中作为癌基因已被广泛报道，并且它也是一个临床治疗靶点。本研究旨在评估TTK在人骨肉瘤组织中的表达水平及其与骨肉瘤患者临床特征的关系，并评估其在骨肉瘤发生发展中的潜在作用。
采用免疫组织化学（IHC）检测方法，检测了74例骨肉瘤组织及其相应癌旁组织中TTK的表达水平。此外，根据肿瘤组织中TTK的染色强度，将患者分为TTK高表达组和低表达组。分析TTK表达水平与临床特征之间的可能相关性，并通过集落形成实验和细胞计数试剂盒-8（CCK8）实验检测TTK对骨肉瘤细胞增殖的影响。利用动物模型检测TTK对肿瘤生长的影响。
磷酸酪氨酸特异性苏氨酸激酶在人骨肉瘤组织中异常高表达。同时，TTK与骨肉瘤患者的肿瘤大小（P = 0.004*）和临床分期（P = 0.014*）等临床特征显著相关。我们的结果还显示，抑制TTK可显著抑制骨肉瘤细胞的增殖，并阻断小鼠肿瘤的生长。
我们证明了TTK参与了骨肉瘤的发生发展，因此我们建议应将TTK视为骨肉瘤有前景的治疗靶点。
