Spatial characterization and stratification of colorectal adenomas by deep visual proteomics

Colorectal adenomas (CRAs) are potential precursor lesions to adenocarcinomas, currently classified by morphological features. We aimed to establish a molecular feature-based risk allocation framework toward improved patient stratification. Deep visual proteomics (DVP) is an approach that combines image-based artificial intelligence with automated microdissection and ultra-high sensitive mass spectrometry. Here, we used DVP on formalin-fixed, paraffin-embedded (FFPE) CRA tissues from nine male patients, immunohistologically stained for caudal-type homeobox 2 (CDX2), a protein implicated in colorectal cancer, enabling the characterization of cellular heterogeneity within distinct tissue regions and across patients. DVP identified DMBT1, MARCKS, and CD99 as protein markers linked to recurrence, suggesting their potential for risk assessment. It also detected a metabolic shift to anaerobic glycolysis in cells with high CDX2 expression. Our findings underscore the potential of spatial proteomics to refine early stage detection and contribute to personalized patient management strategies and provided novel insights into metabolic reprogramming. [Display omitted] •Single-cell-type spatial proteomics characterizes colorectal adenoma heterogeneity•Metabolic switch to anaerobic glycolysis in high-grade dysplasia regions•DMBT1, MARCKS, and CD99 can stratify adenomas in deep visual proteomics•Proteomics of high-grade dysplasia areas show protein signatures of recurrence Artificial intelligence; Cancer; Cancer systems biology; Proteomics