Identification of HOMER2 as a novel biomarker of endometrial receptivity by Integrated Bioinformatics Analysis

Abstract Endometrial receptivity is a critical factor for successful embryo implantation. Poor receptivity of the endometrium is a significant contributor to recurrent implantation failure (RIF) in assisted reproduction. Therefore, a comprehensive understanding of the molecular mechanisms governing endometrial receptivity is essential for enhancing the success rate of embryo implantation and developing new therapeutic approaches for RIF. In this study, we conducted tissue-wide differential gene expression analysis on three microarray datasets (GSE111974, GSE26787, and GSE188409) comparing RIF and control groups. we also performed differential gene expression analysis of epithelial cells and high-dimensional weighted gene co-expression network analysis on the single-cell dataset GSE183807. By integrating these three gene sets, we identified key genes for RIF. Finally, we used gene score and correlation analyses to explore the relationship between the epithelial-mesenchymal transition (EMT) process and key genes in the menstrual cycle. We employed functional pathway enrichment of genes that were highly correlated with key genes to speculate on the mechanism of action of receptivity of the key genes in the endometrium. The results showed that we obtained 298 differentially expressed genes in whole tissues, 816 differentially expressed genes in epithelial tissues and a key module EC-M7. Additionally, we identified HOMER2 as the key gene through intersection. The expression of HOMER2 was negatively correlated with the activity of epithelial-mesenchymal transition, and the genes strongly positively correlated with HOMER2 were mainly involved in the nucleotide metabolism pathway. We hypothesize that HOMER2 may be involved in the regulation of proliferation, migration and EMT of endometrial epithelial cells, and its low expression in mid-secretory phase may serve as a marker of the establishment of endometrial receptivity. This study provides novel insights into the establishment of endometrial receptivity and provides a scientific basis for potential therapeutic agents for RIF.