Identification of Biomarkers for Precancerous Colorectal Lesions Utilizing Olink Proteomics and Colorectal Cancer Animal Models

Neoplastic polyps are precancerous lesions of colorectal cancer (CRC), yet proteomic studies for stratifying their malignant potential remain limited. In this study, we used the Olink proteomics platform to systematically analyze the expression of inflammation- and oncology-related proteins in colorectal polyp tissues from 94 patients. The results showed that most inflammation- and oncology-related proteins were expressed at higher levels in neoplastic polyps than in non-neoplastic polyps. We further screened differentially expressed proteins using receiver operating characteristic (ROC) curve analysis, random forest, and LASSO regression. These findings were then validated using enzyme-linked immunosorbent assay (ELISA), public transcriptomic and single-cell transcriptomic datasets, and colonic immunohistochemistry (IHC) in colitis-associated colorectal cancer (CAC) and Apcmin/+ mouse models. In addition, 38 intestinal fluid samples were collected for supplementary validation. We ultimately identified ADAM8, WISP-1, MMP-1, and PPY as potential biomarkers of precancerous colorectal lesions. These proteins may provide valuable molecular evidence for deeper mechanistic studies of the CRC precancerous stage, early biomarker discovery, and prevention-oriented therapeutic development.