A Network‐Based Association of IBD and Colorectal Cancer Using Proteomics Data

Background Colorectal cancer (CRC) is a major cause of morbidity and mortality, with chronic inflammation from inflammatory bowel disease (IBD) representing a well‐established risk factor. Clarifying shared molecular mechanisms may facilitate early detection and prevention strategies. Methods Proteomic data from the UK Biobank were analysed using the Olink proximity extension assay for seven CRC‐associated proteins (TFF3, TFF1, AHCY, RETN, LCN2, SELE and CEACAM5) previously identified via machine learning. Expression levels in CRC and IBD cases were compared with controls. Multilayer interaction networks, incorporating protein–protein, protein–metabolite and transcription factor–protein interactions, were generated using OmicsNet. Findings were validated in the Colonomics transcriptomic dataset. Results All seven proteins were significantly upregulated in CRC; six (excluding CEACAM5) were also elevated in IBD. Network analysis identified AHCY and LCN2 as central hubs linking inflammatory and metabolic pathways. NF‐κB and GATA2 emerged as recurrent transcriptional regulators. Colonomics validation confirmed upregulation of AHCY, LCN2 and SELE in CRC tissues. Conclusions This multi‐omics network analysis reveals a shared molecular framework between IBD and CRC, with inflammation as a key driver of colorectal carcinogenesis.