Identification of key genes associated with infertile endometriosis based on bioinformatic analysis

基于生物信息学分析鉴定与不孕症相关的子宫内膜异位症关键基因

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Abstract

BACKGROUND: Endometriosis is a common disease among women of childbearing age. However, the molecular mechanism behind it is still unknown. Therefore, new biomarkers and therapeutic targets are needed to improve the diagnosis and treatment of infertile women. METHODS: Microarray datasets GSE7305, GSE7307, and GSE51981 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between control and endometriosis. The STRING database and Cytoscape software constructed protein-protein interaction and hub gene networks. At the same time, the three data sets were screened for co-differentially expressed genes related to mitosis. Subsequently, we identified mitosis-related hub genes (MRHGs) associated with both mitosis-related genes and hub genes. Next, enrichment analysis for target genes was performed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the mRNA-miRNA network was constructed. Finally, GSE25628 and GSE6364 were used to verify the expression of MRHGs individually, while GSE120103 was employed to ascertain the influence of mitosis-related genes on female fertility. RESULTS: A total of 93 DEGs were identified in the endometriosis datasets. Then, we placed 11 potential mitosis-related downregulated hub genes, among which eight showed good diagnostic properties of endometriosis, and two showed good diagnostic properties of infertile endometriosis. The main enriched GO functions revealed that the cell cycle mitotic pathway may be the critical pathway in endometriosis. Meanwhile, mRNA-miRNA interaction networks were constructed by choosing co-expressed mRNAs and miRNAs. Furthermore, cordycepin showed high drug-targeting relevance in infertile endometriosis. CONCLUSION: We identified eight mitosis-related hub genes as potential biomarkers for diagnosing and treating endometriosis. CENPE and CCNA2 might be associated with infertile endometriosis by affecting the endometrial secretory phase transition. In addition, cordycepin may be a potential clinical treatment for people with infertility-related endometriosis.

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