ArticleFrontiers in immunology2026
LRP1 as a potential diagnostic and immunomodulatory target in endometriosis: evidence from multi-omics and single-cell analyses.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Endometriosis (EMS) is a common gynecological disease that seriously affects women's health and quality of life. However, the detailed dynamic cellular and molecular mechanisms underlying EMS pathogenesis remain largely unknown. This study establishes a novel diagnostic model to distinguish ectopic endometrium (EC) from eutopic endometrium (EU) samples. This study elucidated the critical role of low-density lipoprotein receptor-related protein 1 (LRP1) in EMS pathogenesis through integrated multi-omics analyses. Our comprehensive approach began with merging three GEO datasets (GSE7305, GSE11691, GSE25628), identifying 1,404 differentially expressed genes (DEGs) and 489 co-expressed genes with the brown module using weighted gene co-expression network analysis (WGCNA). A machine learning algorithm identified 30 hub genes, among which LRP1 exhibited the highest diagnostic performance. Immune profiling revealed a strong positive correlation between LRP1 and M2 macrophage infiltration (r=0.62, p<0.001), while Mendelian randomization analysis confirmed a causal relationship (OR = 1.35, 95%CI:1.13-1.61, p=0.001). Single-cell RNA sequencing demonstrated LRP1 is predominantly expressed in fibroblasts and monocytes, orchestrating cell-cell communication through the MIF signaling pathway, particularly through CD74/CXCR4 interactions. Experimental validation confirmed significantly elevated LRP1 expression in ectopic lesions at both mRNA (p<0.01) and protein levels. Mechanistically, LRP1 may promote the progression of EMS by enhancing cell migration, invasion, and proliferation through the MIF signaling pathway. Collectively, these findings identified LRP1 as a central regulator of EMS progression through immunomodulation and intercellular crosstalk, offering novel diagnostic and therapeutic potential.
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