Frontiers in immunology
An SPP1-centered immune-parenchymal communication axis links macrophage heterogeneity to ovarian cancer prognosis
By Liu X, Xia L, Sheng J and 2 others.
Abstract
Background
Immune and malignant epithelial cells shape each other through ligand-receptor signaling in ovarian cancer. SPP1 interacts with CD44 and several integrins, but its cellular organization and clinical relevance remain unclear.
Methods
We integrated GSE184880 scRNA-seq data with TCGA-OV and three independent cohorts. Single-cell clustering, CNV inference, and cell communication analysis were used to characterize macrophage states and SPP1-related signaling. Based on the SPP1 ligand-receptor network identified by CellChat, an 11-gene set comprising SPP1 and its CD44/integrin receptor components was constructed and subsequently used for molecular subtyping. Four machine learning models were compared for prognostic prediction. PI3 was subsequently silenced in ES-2 and SKOV3 cells. SPP1 expression and secretion, cell proliferation, wound closure, migration, invasion, xenograft growth, and macrophage phenotypes after coculture were then evaluated.