微创医学

目的基于加权基因共表达网络筛选影响子宫内膜癌发生发展的关键基因并分析其与预后的关系。方法从美国国立生物技术信息中心基因表达综合数据库中下载包含子宫内膜癌组织和正常内膜组织样本数据集（GSE17025）的基因芯片表达数据。使用R 4.2.1软件中的Limma包筛选出差异表达基因，并利用WGCNA包构建基因共表达网络，获得相关模块及其基因集，然后利用Venn包对相关系数最大的模块基因和差异表达基因取交集。对交集基因进行基因本体论(GO)分析、京都基因与基因组百科全书(KEGG)通路富集分析，并构建交集基因的蛋白-蛋白互作（PPI）网络，采用Cytoscape 软件提取出关键基因，分析关键基因与子宫内膜癌预后的关系。结果共筛选出差异表达基因2 165个，包含5个模块，其中红色模块（包括304个基因）与子宫内膜癌的相关度最高（r=-0.54，P＜0.001），取二者交集获得137个基因。交集基因主要涉及细胞器分裂及核分化等生物学过程，且主要富集在同源重组、p53信号通路等信号通路中。PPI网络共筛选出7个关键基因，包括纺锤体样小头畸形相关蛋白基因（ASPM）、丝氨酸/苏氨酸蛋白激酶（BUB1）、丝氨酸/苏氨酸蛋白激酶B（BUB1B）、细胞分裂周期20（CDC20）、驱动蛋白家族成员11（KIF11）、细胞周期蛋白依赖性激酶1（CDK1）和拓扑异构酶Ⅱα（TOPⅡ α），其中6个基因（ASPM、BUB1、BUB1B、CDC20、 KIF11和TOPⅡ α）的高表达与预后较差有关。结论ASPM、BUB1、BUB1B、CDC20、KIF11、CDK1和TOPⅡ α可能是影响子宫内膜癌发生发展的关键基因，其中ASPM、BUB1、BUB1B、CDC20、 KIF11和TOPⅡ α基因的高表达与预后较差有关。

ObjectiveTo screen key genes affecting the occurrence and development of endometrial cancer based on weighted gene co-expression network and analyze their relationship with prognosis. MethodsGenetic chip expression data containing the endometrial cancer tissue and normal endometrial tissue sample dataset (GSE17025) were downloaded from gene expression omnibus data base of USA National Center for Biotechnology Information. Differentially expressed genes were screened out by Limma package in R 4.2.1 software, and gene co-expression network was constructed by the WGCNA package to obtain the related modules and their gene sets, and then the module genes with the largest correlation coefficient and the differentially expressed genes were intersected by Venn package. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analysis were performed on the intersecting genes, and a protein-protein interaction (PPI) network of the intersecting genes were constructed. And Cytoscape software was used to extract key genes and analyze the relationship between key genes and prognosis of endometrial carcinoma. ResultsA total of 2 165 differentially expressed genes were screened out, including 5 modules, among which the red module (including 304 genes) had the highest correlation with endometrial cancer (r=-0.54, P＜0.001), and 137 genes were obtained from the intersection of the two. The intersecting genes were mainly involved in biological processes such as organelle division and nuclear differentiation, and were mainly enriched in signaling pathways such as homologous recombination and p53 signaling pathway. Seven key genes were screened out by PPI network, including abnormal spindle-like microcephaly (ASPM)-associated protein genes, budding uninhibited by benzimidazoles-1 (BUB1), budding uninhibited by benzimidazoles-1 beta (BUB1B), cell division cycle 20 (CDC20), kinesin family member 11 (KIF11), cyclin dependent kinase 1 (CDK1) and topoisomerase Ⅱ alpha (Topo Ⅱ α). High expression of 6 genes (ASPM, BUB1, BUB1B, CDC20, KIF11 and Topo Ⅱ α) was associated with poor prognosis. ConclusionASPM, BUB1, BUB1B, CDC20, KIF11, CDK1, and Topo Ⅱ α may be the key genes affecting the occurrence and development of endometrial cancer, in which high expression of ASPM, BUB1, BUB1B, CDC20, KIF11, and Topo Ⅱ α genes is associated with poor prognosis.