Abstract
Colorectal adenomas are cancer precursor lesions of the large bowel. Using iTRAQ 8‐plex labelling, OFFGEL electrophoresis, and LC‐coupled tandem MS, we investigated the proteome of 30 colorectal adenomas and paired normal mucosal samples (prospectively collected during colonoscopy), and that of normal (HCEC) and cancerous (SW480, SW620, CACO2, HT29, CX1) colon epithelial cell lines. A total of 4325 and 2017 non‐redundant protein families were identified and quantified in tissue and cell lines, respectively. Principal component analysis clearly distinguished adenomas from normal mucosa, and cancer cell lines from HCEC cells. Two hundred twelve proteins displayed significant adenoma‐related expression changes (q‐value<0.02, mean fold change +/‐1.4), which correlated (r=0.74) with similar changes previously identified by our group at the transcriptome level. Fifty one proteins displayed directionally similar expression changes in colorectal cancer cells (vs HCEC cells) and were therefore attributed to the epithelial component of adenomas. Although benign, adenomas already exhibited protein expression changes previously documented only in advanced colorectal cancers. They also disclosed several novel changes with potentially important roles in early‐stage large bowel tumorigenesis, including the marked upregulation of a key enzyme in the polyol pathway.Grant Funding Source: Supported by the Swiss National Science Foundation
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