Cancer Proteomics in Human CRC Epithelial Cells: A Real Potential or Just Another Wishful Thinking?
By Chin Siok-Fong (chinsiokfong@ppukm.ukm.edu.my)
Over recent years, numerous proteomics data have been published on colorectal cancer (CRC) but results remain controversial as there are serious concerns regarding reproducibility issues; among them, poorly characterized samples using whole tissue biopsies. The need to control for homogeneity of sample phenotypes is inevitable for protein profiling. By overcoming heterogeneity issues, differences observed in protein expression can be confidently related to heterogeneity of the clinical behaviour of the cancer and hence can be used as prognostic factors. Epithelial cells are thought to be an excellent study model as they follow a systematic process of cellular proliferation, differentiation, adenoma formation and eventually cancer transformation. In this study, immuno-isolated epithelial cells from human cancerous and normal colon tissues were lysed and subjected to protein reduction, alkylation and tryptic digestion. MS/MSALL with SWATH Acquisition was applied as a powerful strategy for quantitative profiling of a large number of proteins in the investigation. Principal component analysis (PCA) across the multiple samples revealed distinct clusters corresponding to state of the disease with additional comparison against some cultured cell lines. Three exclusively expressed structural proteins were identified in the samples from the early stages of CRC. Pathway Analysis uncovered upregulations of both Metabolic and Ribosome Pathways in the CRC epithelial cells whereas Pathway Mapping on the significant differentially expressed proteins suggests the involvement of Heat Shock Proteins in tumorigenicity of the cells. In summary, epithelial cells can be an outstanding model to study proteomics in CRC.
