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Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: Importantly, our findings may contribute to the scientific basis for several potential therapeutic agents to improve endometrial receptivity.

 

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Title: Comprehensive Analysis of Differentially Expressed Genes and Immune Infiltration in Recurrent Implantation Failure: Implications for Diagnosis and Therapeutics

Abstract:

Recurrent Implantation Failure (RIF) poses a significant challenge in reproductive medicine, and its elusive etiology has motivated investigations into potential molecular mechanisms. In this study, we utilized gene expression datasets (GSE103465 and GSE111974) to identify Differentially Expressed Genes (DEGs) in the endometrium, comparing RIF patients to healthy controls. Our comprehensive analysis involved Gene Ontology, Kyoto Encyclopedia of Genes and Genomes Pathway, Gene Set Enrichment, and Protein-Protein Interactions analyses to elucidate the biological functions and signaling pathways associated with RIF.

The exploration of immune cell infiltration using CIBERSORT unveiled significant alterations in the immune landscape of RIF. Flow cytometry validation of the top two immune cell types confirmed the reliability of our findings. Notably, we identified 122 downregulated and 66 upregulated DEGs, with a focus on six immune-related hub genes intricately linked to Wnt/β-catenin and Notch signaling pathways. ROC curve analysis highlighted three genes (AKT1, PSMB8, and PSMD10) as potential diagnostic markers for RIF.

Moreover, our study delved into the therapeutic realm, employing cMap analysis to identify compounds with potential efficacy against RIF. Fulvestrant, a known estrogen receptor antagonist, along with bisindolylmaleimide-ix (CDK and PKC inhibitor) and JNK-9L (JNK inhibitor), emerged as promising candidates influencing the pathogenic processes of RIF.

In conclusion, this research provides a deeper understanding of the molecular landscape of RIF, shedding light on immune infiltration, key signaling pathways, and potential diagnostic markers. The identified therapeutic compounds offer a glimpse into novel avenues for improving endometrial receptivity, holding promise for the development of targeted interventions in the management of RIF.

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Cat.No. Product Name Information
S7207 Bisindolylmaleimide IX (Ro 31-8220) Mesylate Bisindolylmaleimide IX (Ro 31-8220 Mesylate) is a pan-PKC inhibitor with IC50 of 5 nM, 24 nM, 14 nM, 27 nM, and 24 nM for PKC-α, PKC-βI, PKC-βII, PKC-γ, and PKC-ε, respectively, and also shows potent inhibition against MAPKAP-K1b, MSK1, GSK3β and S6K1.

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PKC