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pmid:36911409
Gene profiling reveals the role of inflammation, abnormal uterine muscle contraction and vascularity in recurrent implantation failure.
Xinyi Dong · Mi Zhou · Xinyu Li · Huijing Huang · Yun Sun
Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1108805
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Experiment
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Complete file
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And the endometrial factors are crucial causes of recurrent implantation failure. However, its mechanism is still unclear. Thus, the aim of this study is to identify altered biologic processes in endometrium that may contribute to recurrent implantation failure. Methods: We recruited two microarray datasets (GSE103465, GSE111974) from Gene Expression Omnibus database (GEO), which contain endometrium from RIF and normal women during implantation period. Using the online tools GEO2R and Venny, we identified Differentially Expressed Genes (DEGs) of selected datasets, and obtained common DEGs. Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCatar pathway enrichment were conducted with Enrichr platform, \"ssgsea\" and \"ggplot2\" package of RStudio. PPI networks and hub gene related TF-gene interaction and TF-miRNA co-regulation networks were built via online tools STRING and NetworkAnalyst. Immune infiltration analysis was performed by CIBERSORT platform. Recurrent implantation failure subgroup identification was achieved through \"ConsensusClusterPlus,\" \"tsne,\" \"ssgsea\", and \"ggpubr\" package in RStudio. Diagnostic characteristic ROC curves were constructed via \"pROC\" and \"ggplot2\" package of RStudio. Enrichr platform was utilized to find drugs targeting hub genes. Results: 26 common DEGs were confirmed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes/BioCarta analysis determined common DEGs were mainly enriched in inflammation associated pathways including TNF, NF-κB, IL-4, IL-10, IL-6, and TGF-β signaling pathways. Five hub genes (PTGS2, VCAM1, EDNRB, ACTA2, and LIF) and related TF-gene and TF-miRNA interactions were identified. Immune infiltration analysis indicated the importance of macrophage M2 in recurrent implantation failure patients. Importantly, subgroup identification analysis highlighted that recurrent implantation failure patients can be divided into two subgroups with different phenotypes. Moreover, the ROC curves and drugs may provide new diagnostic and therapeutic thought for recurrent implantation failure.", "claims": [{"id": "claim-method", "statement": "Using the online analysis tool GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/), the expression profiles of endometrium from RIF patients and fertile women were compared to screen the DEGs of the two datasets, independently. p values were calculated through t-tests and genes with the criteria of a |log2 (fold-change)| >1 and p-value < 0.05 were considered as DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36911409", "locator": "sections[4] \"Analysis for DEGs\" paragraph 2", "quote": "Using the online analysis tool GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r/), the expression profiles of endometrium from RIF patients and fertile women were compared to screen the DEGs of the two datasets, independently. p values were calculated through t-tests and genes with the criteria of a |log2 (fold-change)| >1 and p-value < 0.05 were considered as DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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