Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
Mol Med Rep. 2018 Jul;18(1):467-476. doi: 10.3892/mmr.2018.8969. Epub 2018 May 4.
Endometrial carcinoma (EC) is one of the most common gynecological malignancies. The malignant degree increases between grade (G)1 and G3, and EC of G3 usually presents a high recurrence rate and poor prognosis. Therefore, the present study aimed to examine the principal genes associated with the degree of differentiation in EC. The microarrays GSE17025, GSE24537 and GSE35784, representing data of Type I EC samples of G1 and G3, were downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) and differentially expressed micro (mi)RNAs (DEMs) were identified, followed by functional enrichment analyses and interaction network construction. In total, 83 upregulated and 130 downregulated DEGs with the same expression trends in two mRNA datasets were screened. The upregulated DEGs were primarily enriched in 'mitotic cell cycle process', 'cell cycle process' and 'mitotic cell cycle'; while the downregulated DEGs were enriched in 'cellular component assembly involved in morphogenesis', 'cell projection organization' and 'microtubule‑based movement'. From the protein‑protein interaction network, DNA topoisomerase IIα, kinesin family member 11, cyclin B1 and BUB1 mitotic checkpoint serine/threonine were identified as foremost hub genes. One module was extracted and involved in 'mitotic cell cycle process' and 'cell cycle process'. Based on the analysis of DEMs and the miRNA‑target regulatory network, miRNA‑9 may be the most important upregulated DEM, and the DEGs forkhead box P1 and cyclin E1 may serve vital roles in the differentiation of EC. In conclusion, principal genes were identified that may be determinants of the carcinogenesis of poorly differentiated EC, which may facilitate the examination of potential molecular mechanisms. These genes may additionally help identify candidate biomarkers and novel therapeutic targets for poorly differentiated EC.
子宫内膜癌(EC)是最常见的妇科恶性肿瘤之一。恶性程度在 G1 到 G3 之间逐渐增加,G3 级 EC 通常具有较高的复发率和较差的预后。因此,本研究旨在探讨与 EC 分化程度相关的主要基因。从基因表达综合数据库中下载 GSE17025、GSE24537 和 GSE35784 微阵列,代表 G1 和 G3 型 I 型 EC 样本的数据。鉴定差异表达基因(DEGs)和差异表达 microRNAs(DEMs),然后进行功能富集分析和互作网络构建。总共筛选出 83 个上调和 130 个下调的 DEGs,这两个 mRNA 数据集的表达趋势相同。上调的 DEGs 主要富集在“有丝分裂细胞周期过程”、“细胞周期过程”和“有丝分裂细胞周期”;而下调的 DEGs 则富集在“细胞成分组装参与形态发生”、“细胞突起组织”和“基于微管的运动”。从蛋白质-蛋白质相互作用网络中,鉴定到 DNA 拓扑异构酶 IIα、驱动蛋白家族成员 11、细胞周期蛋白 B1 和 BUB1 有丝分裂检查点丝氨酸/苏氨酸为最重要的核心基因。提取一个模块,涉及“有丝分裂细胞周期过程”和“细胞周期过程”。基于 DEMs 的分析和 miRNA-靶调控网络,miRNA-9 可能是最重要的上调 DEM,FOXP1 和 cyclin E1 等 DEGs 可能在 EC 分化中发挥重要作用。总之,鉴定出了一些主要基因,这些基因可能是低分化 EC 癌变的决定因素,有助于研究潜在的分子机制。这些基因可能有助于识别低分化 EC 的候选生物标志物和新的治疗靶点。