Immune cell enrichment characteristics and related key genes in intrauterine adhesion: insights from RNA-sequencing analysis.

Abstract

Intrauterine adhesion (IUA) represents a prevalent cause of persistent infertility and continues to be a significant unresolved challenge in reproductive medicine. However, its full pathogenic mechanisms remain incompletely elucidated. We retrieved endometrial RNA-sequencing data from IUA patients and normal controls in the Gene Expression Omnibus (GEO) database, and screened 586 differentially expressed genes (DEGs) in the endometrium of IUA patients using the R package limma. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) revealed activation of immune-related pathways, including chronic inflammatory response, complement activation, and complement and coagulation cascades in IUA. Further single-sample gene set enrichment analysis (ssGSEA)-based relative immune cell enrichment analysis revealed decreased enrichment scores of activated CD4 T cells and type 2 T helper cells, alongside increased enrichment scores of effector memory CD8 T cells, macrophages, mast cells, natural killer cells, and T follicular helper cells in IUA patients, indicating their potential involvement in IUA pathogenesis. A protein-protein interaction (PPI) network was constructed, identifying 10 hub genes associated with IUA: CDK1, CCNB1, CCNA2, CENPA, BUB1, AURKB, KIF11, BUB1B, CDC20, and TOP2A. The expression patterns of these genes were further validated in two independent external IUA cohorts, supporting a potential correlative link between these genes and IUA pathogenesis. Our findings provide exploratory insights and potential candidate molecules for subsequent mechanistic studies of IUA onset and progression.