Spatial transcriptomics reveals two-phase epithelial and immune remodeling in obese colorectal cancer, indicating new targets for risk stratification.
Key Points
To determine how obesity alters the spatial architecture, early epithelial transformation, and immune interactions across pre-neoplastic mucosa and tumors in colorectal cancer.
Analyzed tissue from 89 colorectal cancer patients across 288 annotated regions using GeoMx Digital Spatial Profiling.
Profiled 24 colorectal cancer patients (12 obese, 12 non-obese) across 969 fields of view using CosMx Spatial Molecular Imaging to map cellular interactions across tumor, normal mucosa, adipose, and stromal compartments.
Identified a transcriptionally shifted epithelial state within morphologically intact obese-normal mucosa characterized by two distinct expression trajectories among 30 colorectal cancer-related genes, which persisted into tumor development.
Demonstrated tumor-associated spatial immune remodeling in obesity, marked by localized enrichment of SPP1⁺ macrophages, an increased SPP1⁺ to pro-inflammatory macrophage ratio near cancer cells, and amplified growth-factor and cytokine signaling.