title: Proteomic analysis of urinary upper gastrointestinal cancer markers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: School of Clinical Sciences and Community Health, University of Edinburgh, UK. H.Husi@ed.ac.uk
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.forename: Nathan
authors.initials: N
authors.lastname: Stephens
authors.forename: Andrew
authors.initials: A
authors.lastname: Cronshaw
authors.forename: Alisdair
authors.initials: A
authors.lastname: MacDonald
authors.forename: Iain
authors.initials: I
authors.lastname: Gallagher
authors.forename: Carolyn
authors.initials: C
authors.lastname: Greig
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D016022:Case-Control Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D041742:Upper Gastrointestinal Tract / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor