Cong Shanshan, Guo Qiuyan, Cheng Yan, Gao Jianhua, Sun Liyuan, Wang Jing, Wu Han, Liang Tian, Zhang Guangmei
Department of Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.
Front Mol Biosci. 2021 Jan 7;7:614427. doi: 10.3389/fmolb.2020.614427. eCollection 2020.
Endometriosis is interpreted as the existence of endometrium outside the uterine cavity, such as ovaries, fallopian tubes and pelvic cavity. Dysmenorrhea, abnormal menstruation, infertility, and chronic pelvic pain are the primary symptoms of endometriosis. Although there are many theories about the origin of endometriosis, the exact factor of the disease has not been confirmed. Therefore, many other mechanisms are still worth exploring. The gene lists of the transcription factors (TFs) were selected from the intersections of three databases. The limma R package was used to analyze the differentially expressed genes (DEGs) of GSE6364 and GSE7305 and the DEGs intersected with the TFs to obtain the differentially expressed TFs (DETFs). Subsequently, one-way ANOVA and Student's -test were used to analyze the expression of DETFs in different phases of the endometrium and the endometrium of the infertile and fertile females with endometriosis, respectively. Enrichment analysis and PPI network were performed to reveal the molecular mechanisms of endometriosis. Finally, the plotROC R package was used to evaluate the sensitivity and specificity of hub TFs for the diagnosis of endometriosis. A total of 54 DETFs were screened out in endometriosis. The expression of up-regulated DETFs was gradually increased from the early secretory to the proliferative phase of the endometrium. Most up-regulated DETFs increased expression in the endometrium of infertile females. The pathways of DETFs were mainly enriched in stem cell differentiation, transcription activity, steroid hormone receptor activity and herpes simplex virus. Two hub TFs (RUNX2 and BATF) and two sub-networks were finally acquired from the PPI network. RUNX2 and BATF also had high diagnostic value in endometriosis. We discovered and analyzed 54 DETFs that were closely related to endometriosis, which would contribute to explore new mechanisms of endometriosis and search for new diagnostic markers and effective therapeutic targets.
子宫内膜异位症被解释为子宫腔外存在子宫内膜，如卵巢、输卵管和盆腔。痛经、月经异常、不孕和慢性盆腔疼痛是子宫内膜异位症的主要症状。尽管关于子宫内膜异位症的起源有许多理论，但该疾病的确切病因尚未得到证实。因此，许多其他机制仍值得探索。转录因子（TFs）的基因列表是从三个数据库的交集处选择的。使用limma R包分析GSE6364和GSE7305的差异表达基因（DEGs），并将这些DEGs与TFs进行交集分析，以获得差异表达的TFs（DETFs）。随后，分别使用单因素方差分析和学生t检验分析DETFs在子宫内膜不同阶段以及患有子宫内膜异位症的不孕和有生育能力女性的子宫内膜中的表达。进行富集分析和蛋白质-蛋白质相互作用（PPI）网络分析以揭示子宫内膜异位症的分子机制。最后，使用plotROC R包评估核心TFs对子宫内膜异位症诊断的敏感性和特异性。在子宫内膜异位症中总共筛选出54个DETFs。上调的DETFs的表达从子宫内膜的早期分泌期到增殖期逐渐增加。大多数上调的DETFs在不孕女性的子宫内膜中表达增加。DETFs的通路主要富集在干细胞分化、转录活性、类固醇激素受体活性和单纯疱疹病毒方面。最终从PPI网络中获得了两个核心TFs（RUNX2和BATF）和两个子网。RUNX2和BATF在子宫内膜异位症中也具有较高的诊断价值。我们发现并分析了54个与子宫内膜异位症密切相关的DETFs，这将有助于探索子宫内膜异位症的新机制，并寻找新的诊断标志物和有效的治疗靶点。
