Xi Xiaoxue, Cao Tianyue, Qian Yonghong, Wang Huiling, Ju Songwen, Chen Youguo, Chen Ting, Yang Jian, Liang Biaoquan, Hou Shunyu
Department of Obstetrics and Gynaecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University Suzhou 215002, Jiangsu, China.
Central Laboratory, Nanjing Medica University Affiliated Suzhou Hospital Suzhou 215128, Jiangsu, China.
Am J Cancer Res. 2022 Jul 15;12(7):3303-3317. eCollection 2022.
Epithelial ovarian cancer (EOC), a common tumor of the female reproductive system, ranks first in fatalities among gynecological malignancies. Most patients find tumors at late stage and have extremely poor prognoses, which necessitates improvements in early detection. This study applied bioinformatic methods to identify potential biomarkers of EOC. First, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on differentially expressed genes (DEGs) and hub genes, and a protein-protein interaction (PPI) network was constructed. The network of hub genes was analyzed using GeneMANIA, and an analysis of biological processes was constructed with BINGO. Lastly, hub genes were analyzed for EOC-related oncology using the Oncomine and TCGA databases, and the cBioPortal online platform. Overall, cell division cycle 20 (CDC20) was identified as a key gene in EOC. Short hairpin RNA (shRNA) was used to silence CDC20 to explore its effects on EOC cell proliferation, apoptosis and SRY-related HMG-box 2 (SOX2) expression. DEGs were enriched in pathways related to cell cycle signaling, cancer, progesterone-mediated oocyte maturation, Wnt signaling and P53 signaling. Analysis revealed high expression of CDC20 in EOC tissues and a correlation with histology and tumor grade. CDC20 levels are highest in serous adenocarcinoma, when compared to ovarian clear cell carcinoma, ovarian endometrioid carcinoma and mucinous adenocarcinoma. High CDC20 expression within the tumor is associated with poor EOC prognosis. After silencing , EOC cell proliferation and migration decreased, apoptosis increased, and expression decreased. In conclusion, CDC20 is likely a key biomarker of EOC and may act as an upstream regulator of SOX2 to mediate the SOX2 signaling in the progression of EOC. Future application of CDC20 analysis to early detection may improve prognosis, and it has the potential to be a therapeutic target.
上皮性卵巢癌(EOC)是女性生殖系统常见肿瘤,在妇科恶性肿瘤致死率中居首位。大多数患者在晚期发现肿瘤,预后极差,因此有必要改进早期检测方法。本研究应用生物信息学方法鉴定EOC的潜在生物标志物。首先,对差异表达基因(DEG)和枢纽基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,并构建蛋白质-蛋白质相互作用(PPI)网络。使用GeneMANIA分析枢纽基因网络,并用BINGO构建生物学过程分析。最后,利用Oncomine和TCGA数据库以及cBioPortal在线平台分析枢纽基因与EOC相关肿瘤学的关系。总体而言,细胞分裂周期20(CDC20)被确定为EOC中的关键基因。使用短发夹RNA(shRNA)沉默CDC20,以探讨其对EOC细胞增殖、凋亡和SRY相关高迁移率族盒2(SOX2)表达的影响。DEG富集于与细胞周期信号传导、癌症、孕酮介导的卵母细胞成熟、Wnt信号传导和P53信号传导相关的途径。分析显示,CDC20在EOC组织中高表达,且与组织学和肿瘤分级相关。与卵巢透明细胞癌、卵巢子宫内膜样癌和黏液性腺癌相比,浆液性腺癌中CDC20水平最高。肿瘤内高CDC20表达与EOC预后不良相关。沉默后,EOC细胞增殖和迁移减少,凋亡增加, 表达降低。总之,CDC20可能是EOC的关键生物标志物,可能作为SOX2的上游调节因子,在EOC进展中介导SOX2信号传导。未来将CDC20分析应用于早期检测可能改善预后,并且它有可能成为治疗靶点。