中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (3): 182-191.doi: 10.19401/j.cnki.1007-3639.2021.03.004

• 论著 • 上一篇    下一篇

TTK1在卵巢癌铂类耐药中的生物学功能分析

刘懿萱 1 ,文泽轩 2 ,郭 林 1 ,卢仁泉 1   

  1. 1. 复旦大学附属肿瘤医院检验科,复旦大学上海医学院肿瘤学系,上海 200032 ;
    2. 复旦大学公共卫生学院流行病学教研室,上海 200030
  • 出版日期:2021-03-30 发布日期:2021-04-01
  • 通信作者: 卢仁泉 E-mail: lurenquan@126.com
  • 基金资助:
    国家自然科学基金(82072876,81772774,81772808);上海市科学技术委员会引导项目(17411963500)。

The function of TTK1 in platinum-resistant ovarian cancer

LIU Yixuan 1 , WEN Zexuan 2 , GUO Lin 1 , LU Renquan #br#   

  1. 1. Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200030, China
  • Published:2021-03-30 Online:2021-04-01
  • Contact: LU Renquan E-mail: lurenquan@126.com

摘要: 背景与目的:苏氨酸酪氨酸激酶1(threonine tyrosine kinase 1,TTK1)是纺锤体组装检查点的一个组成部分,确保染色体的正确分离,可能是与化疗敏感性相关的潜在目标分子,但TTK1在铂类药物耐药方面的作用机制仍不清楚。卵巢癌是女性常见的生殖系统恶性肿瘤之一,发病率在妇科恶性肿瘤中排名第三,死亡率排名第一。临床上,卵巢癌的化疗方案中常包含铂类药物,但是随着化疗时间延长,患者容易发生铂类药物耐受,影响其治疗进程和预后。因此,有必要寻找与铂类耐药性有关的基因作为卵巢癌治疗的有效靶点。探讨TTK1与卵巢癌铂类耐药之间的关系。方法:基于大数据生物信息学分析,筛选出与TTK1相互作用的基因,进而探索TTK1相关的生物学功能,并建立耐药机制网络模型。利用GEO芯片分析卵巢癌铂类耐药相关通路。对TTK1敲低的卵巢癌铂类耐药细胞RNA进行测序,分析TTK1与耐药相关通路之间的关系。结果:TTK1参与细胞的有丝分裂、细胞分化等过程,在染色体分离过程中发挥重要作用。TTK1在耐铂类化疗药物的卵巢癌患者中高表达,RNA测序结果进一步展示了卵巢癌铂类耐药的细胞中与TTK1相关的信号通路。结论:TTK1可能通过多种途径使卵巢癌产生耐药现象,基于TTK1抑制剂的联合模式治疗卵巢癌可能成为一种新的治疗模式。

关键词: 苏氨酸酪氨酸激酶1, 卵巢癌, 顺铂

Abstract: Background and purpose: Threonine tyrosine kinase 1 (TTK1) is an integral part of the spindle assembly checkpoint and ensuring the correct separation of chromosomes. TTK1 may be a potential target associated with chemotherapy sensitivity. Ovarian cancer, one of the most common malignant tumors in the female, has the third incidence rate and the first mortality rate among gynecological malignant tumors. Clinically, platinum-containing drugs are commonly used in chemotherapy for ovarian cancer. Patients, however, often develop platinum resistance after long term chemotherapy, which affects their treatment course and prognosis. Therefore, it is necessary to find genes associated with platinum-resistance as effective targets for the treatment of ovarian cancer. The purpose of this study was to investigate the relationship between TTK1 and platinum resistance in ovarian cancer. Methods: The genes interacting with TTK1 were screened out through big data analysis, the biological functions of TTK1 were explored, and a network model of drug resistance mechanisms was established based on the relevant gene functions. Platinum resistance-related pathways in ovarian cancer were analyzed by GEO microarray. The RNA of platinum-resistant ovarian cancer cells with TTK1 knockdown was sequenced to analyze the relationship between TTK1 and drug resistance-related pathways. Results: TTK1 participated in the process of cell mitosis and cell differentiation, and played an important role in the process of chromosome separation. It was found that TTK1 was overexpressed in ovarian cancer patients with platinum resistance, and RNA sequencing results further displayed the signaling pathways associated with TTK1 in platinum-resistant cells of ovarian cancer. Conclusion: TTK1 may participate platinum resistance in ovarian cancer through a variety of pathways, and the combined treatment of ovarian cancer based on TTK1 inhibitors may become a new mode of treatment.

Key words: Threonine tyrosine kinase 1, Ovarian cancer, Platinum