Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.
Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.
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DOI：
10.3389/fimmu.2023.992765
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
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复发性着床失败（RIF）是一个令人沮丧的挑战，因为原因不明。目前的研究旨在根据RIF患者和健康对照之间的免疫细胞浸润特征来鉴定子宫内膜中的差异表达基因（DEG），以及研究RIF中潜在的预后标志物。从基因表达综合数据库获得GSE 103465和GSE 111974数据集，以筛选RIF组和对照组之间的DEG。进行基因本体分析、京都基因百科全书和基因组途径分析、基因集富集分析和蛋白质-蛋白质相互作用分析以研究潜在的生物学功能和信号传导途径。CIBERSORT用于描述RIF中的免疫浸润水平，流式细胞术用于确认检测到的前两种最丰富的免疫细胞。在RIF组和对照组之间获得了122个下调和66个上调的DEG。我们的研究发现了六个免疫相关的hub基因，它们参与Wnt/β-catenin信号传导和Notch信号传导。ROC曲线显示，6个基因中的3个（AKT 1、PSMB 8和PSMD 10）对RIF具有潜在的诊断价值。最后，我们使用cMap分析来鉴定RIF的潜在治疗或诱导化合物，其中氟维司群（雌激素受体拮抗剂）、双吲哚马来酰亚胺-ix（CDK和PKC抑制剂）和JNK-9 L（JNK抑制剂）被认为影响RIF的致病过程。此外，我们的研究结果通过突出三种信号传导途径（Wnt/-catenin信号传导，Notch信号传导和免疫应答）和三种潜在的诊断DEG（AKT 1，PSMB 8和PSMD 10）揭示了RIF中的免疫浸润水平。重要的是，我们的研究结果可能有助于提高子宫内膜容受性的几种潜在治疗药物的科学基础。
Recurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF. GSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, Gene Set Enrichment Analysis, and Protein-protein interactions analysis were performed to investigate potential biological functions and signaling pathways. CIBERSORT was used to describe the level of immune infiltration in RIF, and flow cytometry was used to confirm the top two most abundant immune cells detected. 122 downregulated and 66 upregulated DEGs were obtained between RIF and control groups. Six immune-related hub genes were discovered, which were involved in Wnt/-catenin signaling and Notch signaling as a result of our research. The ROC curves revealed that three of the six identified genes (AKT1, PSMB8, and PSMD10) had potential diagnostic values for RIF. Finally, we used cMap analysis to identify potential therapeutic or induced compounds for RIF, among which fulvestrant (estrogen receptor antagonist), bisindolylmaleimide-ix (CDK and PKC inhibitor), and JNK-9L (JNK inhibitor) were thought to influence the pathogenic process of RIF. Furthermore, our findings revealed the level of immune infiltration in RIF by highlighting three signaling pathways (Wnt/-catenin signaling, Notch signaling, and immune response) and three potential diagnostic DEGs (AKT1, PSMB8, and PSMD10). Importantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.