Purpose: We have investigated the use of human urine as a non-invasive medium to screen for molecular biomarkers of carcinomas of the upper gastrointestinal (uGI) tract using SELDI-TOF-MS. Experimental design: A total of 120 urine specimens from 60 control and 60 uGI cancer patients were analysed to establish a potential biomarker fingerprint for the weak cation exchanger CM10 chip surface, which was validated by blind testing using a further 59 samples from 33 control and 26 uGI cancer patients. Results: Using Biomarker Pattern software, we established a model with a sensitivity of 98% and specificity of 95% for the learning sample set, and a sensitivity of 96% and specificity of 72% for the validation data set. Model variable importance included six peptides with m/z of 10â€‰230, 10â€‰436, 10â€‰574, 10â€‰311, 10â€‰467, and 1â€‰0118 of which the 10â€‰230 molecular species was the main decider (sensitivity 86% and specificity 80. Initial protein database searching identified 10â€‰230 as S100-A6, 10â€‰436 as S100-P, 10â€‰467 as S100-A9, and 10â€‰574 as S100-A12 of which S100-A6 and S100-A9 were confirmed by Western blotting. Conclusions and clinical relevance: We have demonstrated that SELDI-TOF-MS as a screening tool is a rapid and valid methodology in the search for urinary cancer biomarkers, and is potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.
Husi, H., Stephens, N., Cronshaw, A., MacDonald, A., Gallagher, I., Greig, C., ... Ross, J. A. (2011). Proteomic analysis of urinary upper gastrointestinal cancer markers. Proteomics Clinical Applications, 5(5-6), 289-299. https://doi.org/10.1002/prca.201000107