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细胞周期蛋白依赖性激酶亚基2的过表达促进子宫平滑肌肉瘤的肿瘤进展并预示不良预后。

Cyclin-dependent kinase subunit 2 overexpression promotes tumor progression and predicts poor prognosis in uterine leiomyosarcoma.

作者信息

Deng Yupeng, Han Qun, Mei Shuyu, Li Hailing, Yang Fan, Wang Jun, Ge Shuang, Jing Xiaotong, Xu Hui, Zhang Tingguo

机构信息

Institute of Pathology and Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China.

Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):2845-2852. doi: 10.3892/ol.2019.10668. Epub 2019 Jul 25.

Abstract

Cyclin-dependent kinase subunit (CKS) 2 is a member of the CKS family, which plays an important role in the regulation of meiosis and mitosis. Overexpression of CKS2 has been reported in several types of tumors. However, few studies have investigated its role in uterine leiomyosarcoma (ULMS). In the present study, the expression of CKS2 in 38 cases of ULMS and 38 cases of uterine leiomyoma (ULM) was analyzed by immunohistochemistry. Moreover, the functional analysis of CKS2 was performed in ULMS cell lines. A significantly higher expression of CKS2 was found in ULMS tissues than in ULM tissues (P<0.01) and high CKS2 expression was associated with increased tumor size, low progesterone receptor expression and poor prognosis in patients with ULMS. Multivariate Cox regression analysis revealed that CKS2 expression status was an independent predictor of overall survival for ULMS. Furthermore, silencing of CKS2 in ULMS cells inhibited cell proliferation, colony formation, migration and invasion, and resulted in cell cycle arrest. In conclusion, the present study demonstrated that CKS2 may serve as a marker for the differential diagnosis of ULMS and ULM. In addition, it may act as an independent prognostic factor in patients with ULMS, and serve as a novel target for ULMS therapy.

摘要

细胞周期蛋白依赖性激酶亚基(CKS)2是CKS家族的成员,在减数分裂和有丝分裂的调控中起重要作用。已有报道称CKS2在多种肿瘤类型中过表达。然而,很少有研究探讨其在子宫平滑肌肉瘤(ULMS)中的作用。在本研究中,采用免疫组织化学方法分析了38例ULMS和38例子宫平滑肌瘤(ULM)中CKS2的表达情况。此外,还对ULMS细胞系进行了CKS2的功能分析。结果发现,CKS2在ULMS组织中的表达明显高于ULM组织(P<0.01),且CKS2高表达与ULMS患者肿瘤体积增大、孕激素受体表达降低及预后不良相关。多因素Cox回归分析显示,CKS2表达状态是ULMS患者总生存的独立预测因素。此外,沉默ULMS细胞中的CKS2可抑制细胞增殖、集落形成、迁移和侵袭,并导致细胞周期停滞。总之,本研究表明CKS2可作为ULMS和ULM鉴别诊断的标志物。此外,它可能是ULMS患者的独立预后因素,并可作为ULMS治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8461/6704316/ed51bb2943bb/ol-18-03-2845-g00.jpg

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