A Multicellular Coordinated Network Driving Lymphovascular Space Invasion in Endometrioid Endometrial Carcinoma

作者：Guo W, Liu T, Ren R, Li N, Zhang W, Si J, Piao Y, Hu Y · 发表于：Cell proliferation · 年份：2026 · DOI：10.1111/cpr.70246

Lymphovascular space invasion (LVSI) is a critical factor linked to metastasis and poor outcomes in endometrioid endometrial carcinoma (EEC), yet its multicellular mechanisms remain unclear. Using single-cell RNA sequencing of 3 LVSI-present (LVSI+) EECs, 2 LVSI-absent (LVSI-) EECs, and 2 normal endometrial samples, we delineated the cellular ecosystems underlying LVSI. LVSI+ EECs exhibited marked epithelial reprogramming, transitioning from differentiated ciliated epithelium to hyperproliferative and metabolically remodelled phenotypes, and contained TC4, a metastatic epithelial subset characterized by hypoxia, partial epithelial-mesenchymal transition, immunosuppression, and progesterone resistance. We also identified nine key genes in malignant epithelial cells associated with LVSI prognosis. The tumour microenvironment in LVSI+ EECs shifted from an inflammatory state dominated by epithelial cells to a collaborative network involving stromal and immune cells. This network was enriched in immunosuppressive ZNF683 + SOX4 + CD8+ T cells, Cycling_T cells, SPP1 + MMP9 + Mac, WNT5A_mCAF, Tip endothelial cells, and lymphatic endothelial cells. WNT5A_mCAF and SPP1 + MMP9 + Mac synergistically remodelled the extracellular matrix, promoted lymphangiogenesis and angiogenesis, and, together with endothelial cells, suppressed T-cell activity via LGALS9-HAVCR2/CD44 inhibitory signalling, thereby establishing a niche conducive to vascular invasion. Using spatial multiplex immunofluoresce...