Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction

Abstract

Background: In recent years, alterations in lipid metabolism are currently considered a hallmark feature of many diseases. However, the role in women with reproductive dysfunction (WRD) remains to be fully elucidated. Here, this study aimed to explore the effect of lipid metabolism-related genes (LMRGs) on endometrial receptivity of WRD.

Methods: This study retrospectively analyzed endometrial receptivity array (ERA) in GEO database. The differential expression genes (DEGs) were obtained by limma differential analysis, and the core genes and corresponding predicted microRNA were obtained through protein-protein interaction (PPI) analysis and TargetScan database, so as to predict the chemical targets of drug therapy. Through the intersection of DEGs and LMRGs, the target gene expression profile was obtained for subsequent consensus clustering analysis and immune analysis. In addition, the immune cell infiltration was assessed by applying the ESTIMATE and MCPcounter algorithm and potential drug targets were obtained from the HERB website.

Results: 1473 genes showed differential expression between the groups of WRD and fertile women, and then a large number of lipid metabolism-related pathways and immune-related pathways were enriched. Twelve core genes and corresponding predicted miR-134-3p were obtained; most importantly, we found that these 12 genes were all LMRGs. Through drug target prediction, we obtained three drugs that regulate lipid metabolism and improve blood circulation, namely lovastatin, estrogen, and quercetin. EHHADH (AUC = 0.85) and PTEN (AUC = 0.82) have the best diagnostic performance. UMAP and heatmap revealed large differences between three clusters. LMRGs revealed specific manifestations of WRD in endometrial receptivity and immune microenvironment.

Conclusions: Our study explored the expression pattern of LMRGs in endometrium of WRD, screened the corresponding biomarkers, and proposed the combination of traditional Chinese and Western medicine to improve the endometrial receptivity.

Keywords: Bioinformatics; Endometrial receptivity; Immune infiltration; Lipid metabolism-related genes; Reproductive dysfunction.