4. Identification of distinctive protein expression patterns in colorectal adenoma

Background As a precursor lesion, adenoma is ideally suited for proteome profiling to investigate early colorectal cancer (CRC) development. The ability to recognise premalignant lesions may have important applications in cancer prevention. Aim To identify protein expression patterns that can distinguish colorectal adenoma from normal tissue. Methods Twenty paired samples of adenoma and normal mucosa were analysed by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MALDI-TOF/TOF MS) to detect proteins with ≥ 2-fold differential expression. Protein expression was validated and localised by immunohistochemistry (IHC). Results 2-DE identified four up-regulated (Annexin A3, S100A11, S1 00P and eIF5A-1)and three down-regulated (Galectin-1, S100A9 and FABPL) proteins in adenomas. These proteins have important functions in cell differentiation, proliferation and metabolism.The finding of decreased S100A9 and galectin-1 expression in adenoma was unexpected given the previous reports of their up-regulation in CRC. Our observations however, were validated by IHC and explained by the cellular localisation of these proteins, which are linked to tumour-associated inflammatory and stromal responses respectively, features seen in CRC but not in adenoma. Conclusions Proteomic study of adenomas provides unique biomolecular insights into early colorectal carcinogenesis, however findings need to be validated and interpreted in the light of IHC tissue localisation. This study identifies a distinctive pattern of protein expression that differentiates colorectal adenoma from both CRC and normal mucosa.