Chen Pei, Yao Mengyun, Fang Tao, Ye Chaoshuang, Du Yongjiang, Jin Yang, Wu Ruijin
Department of Obstetrics and Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Pharmgenomics Pers Med. 2022 Apr 22;15:377-392. doi: 10.2147/PGPM.S354957. eCollection 2022.
Endometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis.
Three endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes.
Among the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions.
This study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.
子宫内膜异位症（EMS）是一种常见且复发率高的妇科疾病，其特征为慢性疼痛和不孕。由于发病机制尚未明确，目前尚无针对子宫内膜异位症的确切治疗方法。本研究旨在通过综合生物信息学分析确定与EMS相关的功能模块和枢纽基因。
从基因表达综合数据库（GEO）获取了三个子宫内膜异位症表达谱系列（GSE25628、GSE23339和GSE7305）。通过加权基因共表达网络分析（WGCNA）构建与EMS相关的模块，随后进行基因本体（GO）富集分析。使用Cytohubba和Cytoscape的MCODE插件筛选枢纽基因，并通过受试者工作特征（ROC）曲线进行验证。进行免疫组织化学以验证枢纽基因在异位子宫内膜组织中的蛋白表达。此外，使用CIBERSORT分析免疫细胞浸润丰度与枢纽基因表达之间的关系。
在获得的18个模块中，暗品红色模块被确定为与EMS相关的模块，其基因显著富集于与细胞迁移和神经发生相关的术语。通过Cytoscape筛选出NFASC和CHL1并将其列为枢纽基因，并证实在异位子宫内膜样本中差异上调。最后，枢纽基因的表达与免疫细胞浸润丰度相关。NFASC或CHL1的高表达与异位病变中M2巨噬细胞增加和自然杀伤（NK）细胞减少相关。
本研究为子宫内膜异位症发病机制的分子因素提供了新的见解，并为NFASC和CHL1这两个枢纽基因未来可能成为新型生物标志物和治疗靶点提供了理论依据。
