Zhang Ying, Zhang Wei, Li Xinglan, Li Dapeng, Zhang Xiaoling, Yin Yajie, Deng Xiangyun, Sheng Xiugui
Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, 440 Jiyan Road, Jinan, 250117, Shandong, People's Republic of China.
School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, 106 Jiwei Road, Jinan, 250022, Shandong, People's Republic of China.
Arch Gynecol Obstet. 2016 Jun;293(6):1287-95. doi: 10.1007/s00404-015-3886-8. Epub 2015 Oct 5.
Endometrial cancer (EC) is the most prevalent malignancy worldwide. Although several efforts had been made to explore the molecular mechanism responsible for EC progression, it is still not fully understood.
To evaluate the clinical characteristics and prognostic factors of patients with EC, and further to search for novel genes associated with EC progression.
We recruited 328 patients with EC and analyzed prognostic factors using Cox proportional hazard regression model. Further, a gene expression profile of EC was used to identify the differentially expressed genes (DEGs) between normal samples and tumor samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis ( http://www.genome.jp/kegg/ ) for DEGs were performed, and then protein-protein interaction (PPI) network of DEGs as well as the subnetwork of PPI were constructed with plug-in, MCODE by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes database.
Our results showed that body mass index (BMI), hypertension, myometrial invasion, pathological type, and Glut4 positive expression were prognostic factors in EC (P < 0.05). Bioinformatics analysis showed that upregulated DEGs were associated with cell cycle, and downregulated DEGs were related to MAPK pathway. Meanwhile, PPI network analysis revealed that upregulated CDK1 and CCNA2 as well as downregulated JUN and FOS were listed in top two nodes with high degrees.
Patients with EC should be given more focused attentions in respect of pathological type, BMI, hypertension, and Glut4-positive expression. In addition, CDK1, CCNA2, JUN, and FOS might play important roles in EC development.
子宫内膜癌(EC)是全球最常见的恶性肿瘤。尽管已经做出了多项努力来探索导致EC进展的分子机制,但仍未完全了解。
评估EC患者的临床特征和预后因素,并进一步寻找与EC进展相关的新基因。
我们招募了328例EC患者,并使用Cox比例风险回归模型分析预后因素。此外,利用EC的基因表达谱来鉴定正常样本和肿瘤样本之间的差异表达基因(DEGs)。随后,对DEGs进行京都基因与基因组百科全书通路富集分析(http://www.genome.jp/kegg/),然后通过插件MCODE将DEGs映射到相互作用基因检索工具数据库中,构建DEGs的蛋白质-蛋白质相互作用(PPI)网络以及PPI子网。
我们的结果表明,体重指数(BMI)、高血压、肌层浸润、病理类型和Glut4阳性表达是EC的预后因素(P<0.05)。生物信息学分析表明,上调的DEGs与细胞周期相关,下调的DEGs与MAPK通路相关。同时,PPI网络分析显示,上调的CDK1和CCNA2以及下调的JUN和FOS位列前两个高度节点。
应更加关注EC患者的病理类型、BMI、高血压和Glut4阳性表达。此外,CDK1、CCNA2、JUN和FOS可能在EC发展中发挥重要作用。