Xu Tao, Dong Menglu, Wang Zhi, Li Hanning, Li Xingrui
Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of HUST, Wuhan, Hubei 430030, People's Republic of China.
Department of Obstetrics and Gynecology, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College of HUST, Wuhan, Hubei 430030, People's Republic of China.
Cancer Manag Res. 2020 Jul 14;12:5773-5786. doi: 10.2147/CMAR.S253349. eCollection 2020.
Ovarian cancer is a major gynecologic malignancy that is often detected at a late stage due to the lack of detailed studies on its pathogenesis and reliable biomarkers for predicting its prognosis.
Four ovarian cancer data sets GSE18520, GSE27651, GSE40595, and GSE52037 were downloaded from the Gene Expression Omnibus (GEO) database and the robust rank aggregation approach was used to find common differentially expressed genes (DEGs). Cytoscape software was used to construct and detect key models of protein-protein interaction (PPI) network. While the expression, prognostic value and potential mechanism of the hub gene non-SMC condensin I complex subunit G (NCAPG) was carried out through Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter online dataset and gene set enrichment analysis. To further investigate the role of NCAPG in ovarian cancer, in vitro experiments were carried out.
A total of 232 DEGs were identified in the four GEO datasets; and we detected 32 hub genes from the PPI network and 21 of these genes were associated with ovarian cancer prognosis, one of which was NCAPG. NCAPG was significantly upregulated in most of the ovarian cancer samples. High NCAPG expression was mainly involved in homologous recombination, DNA replication, proteasome, and more correlated pathways. NCAPG knockdown arrested the cell cycle, inhibited the proliferation, and attenuated the migration ability of A2780 cells. Meanwhile, silencing of NCAPG significantly promoted cisplatin-induced apoptosis thus increased the sensitivity to cisplatin.
NCAPG together with the other 31 hub genes play a vital role in the tumorigenesis of ovarian, meanwhile, the cell cycle pathway may be a potential pathway contributing to progression in OC; and NCAPG expression can be used as a promising target for the treatment of OC.
卵巢癌是一种主要的妇科恶性肿瘤，由于对其发病机制缺乏详细研究以及缺乏预测其预后的可靠生物标志物，卵巢癌往往在晚期才被发现。
从基因表达综合数据库（GEO）下载了四个卵巢癌数据集GSE18520、GSE27651、GSE40595和GSE52037，并采用稳健秩聚合方法寻找共同的差异表达基因（DEG）。利用Cytoscape软件构建并检测蛋白质-蛋白质相互作用（PPI）网络的关键模型。通过基因表达谱交互式分析、Kaplan-Meier绘图仪在线数据集和基因集富集分析，对中心基因非SMC凝聚素I复合体亚基G（NCAPG）的表达、预后价值和潜在机制进行了研究。为了进一步研究NCAPG在卵巢癌中的作用，进行了体外实验。
在四个GEO数据集中共鉴定出232个DEG；我们从PPI网络中检测到32个中心基因，其中21个基因与卵巢癌预后相关，其中之一是NCAPG。NCAPG在大多数卵巢癌样本中显著上调。高NCAPG表达主要参与同源重组、DNA复制、蛋白酶体等相关途径。敲低NCAPG可使细胞周期停滞，抑制A2780细胞的增殖，并减弱其迁移能力。同时，沉默NCAPG可显著促进顺铂诱导的细胞凋亡，从而增加对顺铂的敏感性。
NCAPG与其他31个中心基因在卵巢癌的发生发展中起着至关重要的作用，同时，细胞周期途径可能是促进卵巢癌进展的潜在途径；NCAPG表达可作为卵巢癌治疗的一个有前景的靶点。
