Cui Ding, Liu Yang, Ma Junyan, Lin Kaiqing, Xu Kaihong, Lin Jun
Department of Laboratory, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Gynecology and Obstetrics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
PeerJ. 2020 Dec 7;8:e10171. doi: 10.7717/peerj.10171. eCollection 2020.
The purpose of this study was to integrate the existing expression profile data on endometriosis (EM)-related tissues in order to identify the differentially expressed genes. In this study, three series of raw expression data were downloaded from GEO database. Differentially expressed genes (DEGs) in three tissue types were screened. GO, KEGG pathway enrichment analysis, core differential genes (CDGs) protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) were performed, finally, the dysregulation of Hippo pathway in ectopic endometrium (EC) was detected by Western blotting. A total of 1,811 DEGs between eutopic (EU) and normal endometrium (NE), 5,947 DEGs between EC and EU, and 3,192 DEGs between EC and NE datasets were identified. After screening, 394 CDGs were obtained, and 5 hub genes identified in the PPI network. CDGs enrichment and WGCNA network analysis revealed cell proliferation, differentiation, migration and other biological processes, Hippo and Wnt signaling pathways, and a variety of tumor-related pathways. Western blotting results showed that YAP/TAZ was upregulated, and MOB1, pMOB1, SAV1, LATS1 and LATS2 were downregulated in EC. Moreover, CDGs, especially the hub genes, are potential biomarkers and therapeutic targets. Finally, the Hippo pathway might play a key role in the development of endometriosis.
本研究的目的是整合现有的子宫内膜异位症（EM）相关组织的表达谱数据，以鉴定差异表达基因。在本研究中，从基因表达综合数据库（GEO数据库）下载了三个系列的原始表达数据。筛选了三种组织类型中的差异表达基因（DEG）。进行了基因本体（GO）、京都基因与基因组百科全书（KEGG）通路富集分析、核心差异基因（CDG）的蛋白质-蛋白质相互作用（PPI）网络和加权基因共表达网络分析（WGCNA），最后通过蛋白质免疫印迹法检测了异位子宫内膜（EC）中Hippo通路的失调。在正常子宫内膜（NE）与在位内膜（EU）之间共鉴定出1811个DEG，在EC与EU之间鉴定出5947个DEG，在EC与NE数据集之间鉴定出3192个DEG。筛选后，获得了394个CDG，并在PPI网络中鉴定出5个枢纽基因。CDG富集和WGCNA网络分析揭示了细胞增殖、分化、迁移等生物学过程、Hippo和Wnt信号通路以及多种肿瘤相关通路。蛋白质免疫印迹结果显示，在EC中YAP/TAZ上调，而MOB1、pMOB1、SAV1、LATS1和LATS2下调。此外，CDG，尤其是枢纽基因，是潜在的生物标志物和治疗靶点。最后，Hippo通路可能在子宫内膜异位症的发生发展中起关键作用。
