Tumor-derived Endothelial Cell: Important Etiological Factors in Endometriosis

Endometriosis (EMS) is a very complex disease with high heterogeneity. Recently, single-cell RNA sequencing (scRNA-seq) has been applied to comprehensively characterize cellular heterogeneity. Here, we built a new transcriptomic profile of EMS cellular signatures. Three women diagnosed with endometriosis were recruited. Their fresh eutopic endometrium (EM) and ectopic endometrium (EC) tissues were sampled during surgery. ScRNA-seq was performed on 10x Genomics Chromium. Thirty cell clusters were identified as more than ten different cell types using cell type-specific marker genes. Re-clustering analysis revealed five subtypes of endothelial cells (ECs). Compared to EM, the proportion of tumor-derived ECs (IGFBP3+) was significantly increased in EC (43.8 vs. 16.0%). 63 differentially expressed genes (DEGs) between tumor-derived ECs and normal ECs were enriched in “angiogenesis”, such as EFNB2, DLL4, and THSD7A. Subsequently, 114 retrospective EMS cases were included in clinical validation studies of EFNB2. It was co-expressed with PECAM1 and IGFBP3 and significantly increased in EC. Meanwhile, the recurrence rate of women with EFNB2++ expression was significantly higher than that of EFNB2+ cases (p <0.05). The significant increase in tumor-derived ECs characterized by neovascularization may be an important pathological feature of EMS. In addition, EFNB2 plays an important role and is closely related to the recurrence of EMS.