Multi-omics proposes a complement-adhesion-stromal-vascular (CASVR) framework in chronic rhinosinusitis with nasal polyps

Type 2 inflammation is central to chronic rhinosinusitis with nasal polyps (CRSwNP), but it does not fully explain persistent stromal and vascular remodeling. We asked whether complement, adhesion, stromal, and vascular signals converge across tissue, cellular, and spatial scales. We integrated four bulk-transcriptomic cohorts with a single-cell atlas and GeoMx spatial transcriptomics. Network analysis identified eight contrast-associated hub genes and an ABCC9-ACTA2-GPM6A score that separated study-defined groups across cohorts. Single-cell mapping localized these genes mainly to pericytes, fibroblasts, and endothelial cells, while CellChat linked structural and immune compartments through extracellular-matrix and inflammatory signals. In spatial data, C3-C3AR1 showed closer-than-random proximity after multiple-testing correction, whereas ICAM1-ITGAL/ITGB2 did not. Anatomical-site sensitivity analyses retained all eight hub-gene directions. These findings support CASVR as an association framework linking complement-related signals to structural-vascular compartments and identify C3-C3AR1 for independent mechanistic testing.