Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, China.
NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China.
Front Immunol. 2023 Jan 26;14:992765. doi: 10.3389/fimmu.2023.992765. eCollection 2023.
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.
反复着床失败（RIF）是一个令人沮丧的挑战，因为其病因不明。本研究旨在基于 RIF 患者和健康对照组之间的免疫细胞浸润特征，鉴定子宫内膜中的差异表达基因（DEGs），并探讨 RIF 中的潜在预后标志物。
从基因表达综合数据库中获取 GSE103465 和 GSE111974 数据集，以筛选 RIF 组和对照组之间的 DEGs。进行基因本体分析、京都基因与基因组百科全书通路分析、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通路。使用 CIBERSORT 描述 RIF 中的免疫浸润水平，并使用流式细胞术确认检测到的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 DEGs。通过我们的研究发现了 6 个与免疫相关的枢纽基因，它们涉及 Wnt/-catenin 信号和 Notch 信号。ROC 曲线显示，在这 6 个鉴定的基因中，有 3 个（AKT1、PSMB8 和 PSMD10）具有 RIF 的潜在诊断价值。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）、双吲哚基马来酰亚胺-ix（CDK 和 PKC 抑制剂）和 JNK-9L（JNK 抑制剂）被认为影响 RIF 的发病过程。此外，我们的研究结果通过突出三个信号通路（Wnt/-catenin 信号、Notch 信号和免疫反应）和三个潜在的诊断性 DEGs（AKT1、PSMB8 和 PSMD10），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为几种潜在的治疗药物提供科学依据，以提高子宫内膜的接受性。
