The establishment of screening programmes and the two week wait pathway (2WW) to detect CRC is still largely dependent on invasive and expensive endoscopic/radiological methods. There remains a quest for early detection of colorectal cancer (CRC) using non-invasive methods which are well tolerated and patient acceptable. The aim is to identify putative peptide markers for CRC in urine and plasma.Methods
Urine samples from 12 CRC, 6 colorectal adenomas and 6 controls were evaluated in respect to their peptide profiles by capillary electrophoresis-mass spectrometry (CE-MS). The urinary peptide profiles were compared to those of plasma from another cohort of CRC patients (n=16) and controls (n=17) to search for CRC peptide markers differentially expressed both in blood and urine. This was followed by in silico protease prediction for those CRC peptide markers in plasma for which the amino acid sequence could be resolved.Results
From the 392 plasma and 158 urinary CRC peptide marker candidates, ten were found identical and 16 showed sequence overlap demonstrating their origin from the same protein and protein region. Combining these 26 peptides to a support vector machine classifier resulted in the differentiation of the 12 CRC from the 6 colorectal adenomas and 6 controls with a sensitivity of 1.0 (CI:0.84–1.00) and a specificity of 0.92 (CI: 0.84–1.00) after total cross validation.Conclusions
Peptide identification in urine and plasma shows promise as non-invasive markers for CRC. Further work is underway to validate the specific proteases predicted to be responsible for peptide marker generation at tissue level.