Proteomic Remodelling and Systemic Metabolic Alterations in Serrated Colorectal Lesions: An Exploratory Multi-Omic Study

Serrated colorectal lesions are important precursors of colorectal cancer, but their tissue proteomic and circulating metabolic characteristics remain incompletely defined. This exploratory study contextualised targeted proteomics in 17 paired lesion/non-lesional tissue samples using discovery proteomics from three conventional lesions, and examined two serrated lesions from the same patient (SSL and SSL with high-grade dysplasia). Targeted metabolomics was performed on 27 dried whole-blood spot (DBS) records; 16 patients had linked pre-colonoscopy proteomic and DBS measurements. The 13-protein panel comprised 35 quantified peptides. Within the single-patient SSL comparison, the difference in log2(lesion/non-lesional mucosa) between SSL-HGD and SSL was −0.833 for COL1A1, +0.176 for ITGB1 and +0.037 for RAB11B. Exploratory analysis of 15 inter-omic Spearman correlations revealed nominal associations between RAB11B and Phe/Tyr (rho = 0.612; p = 0.0118) and Val/Phe (rho = −0.518; p = 0.0400); neither remained significant after Benjamini–Hochberg correction. No groupwise DBS difference survived multiplicity correction. These descriptive findings suggest structural and metabolic heterogeneity but do not establish serrated-specific molecular progression, causal inter-omic coupling or clinical biomarker validity.