Proteomic analysis of urinary upper gastrointestinal cancer markers



Husi H, Stephens N, Cronshaw A, MacDonald A, Gallagher IJ, Greig C, Fearon KCH & Ross JA (2011) Proteomic analysis of urinary upper gastrointestinal cancer markers. PROTEOMICS - Clinical Applications, 5 (5-6), pp. 289-299.

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 10,230, 10,436, 10,574, 10,311, 10,467, and 10,118 of which the 10, 230 molecular species was the main decider (sensitivity 86% and specificity 80%). Initial protein database searching identified 10,230 as S100-A6, 10,436 as S100-P, 10,467 as S100-A9, and 10,574 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.

SELDI-TOF; Upper gastrointestinal cancer; Urine biomarker

PROTEOMICS - Clinical Applications: Volume 5, Issue 5-6

Publication date30/06/2011