Understanding prostate cancer progression requires resolving molecular signals in their histological context. We applied an integrated spatial omics framework to clinical prostatectomy specimens spanning distinct histological grades, combining mass spectrometry imaging (MSI), spatial proteomics, and spatial transcriptomics (GeoMx Digital Spatial Profiling) with expert histopathological annotation. MSI delineated grade-associated metabolic landscapes and lipid architectures across tumor, stroma, and glandular compartments, revealing spatially confined metabolic reprogramming at invasive fronts. Spatial proteomics quantified compartment-specific protein networks, highlighting gradients of androgen receptor signaling, immune modulation, and extracellular matrix remodeling that tracked with Gleason pattern complexity. GeoMx profiling captured transcriptomic heterogeneity within annotated regions of interest, uncovering co-localized programs of epithelial plasticity, neuroendocrine features, and immune exclusion in higher-grade lesions.

This presentation demonstrates that coordinated spatial omics with histology provides a high-resolution atlas of prostate cancer’s molecular and microenvironmental complexity, clarifying how heterogeneity and niche interactions drive progression. Our approach establishes a framework for translational deployment of spatial biology in clinical specimens, enabling refined grading and biologically informed stratification in prostate cancer.