title: Programmed cell death 6 interacting protein (PDCD6IP) and Rabenosyn-5 (ZFYVE20) are potential urinary biomarkers for upper gastrointestinal cancer.
abstract: OBJECTIVE
  Cancer of the upper digestive tract (uGI) is a major contributor to cancer-related death worldwide. Due to a rise in occurrence, together with poor survival rates and a lack of diagnostic or prognostic clinical assays, there is a clear need to establish molecular biomarkers.
  
  
  METHODS
  Initial assessment was performed on urine samples from 60 control and 60 uGI cancer patients using MS to establish a peak pattern or fingerprint model, which was validated by a further set of 59 samples.
  
  
  RESULTS
  We detected 86 cluster peaks by MS above frequency and detection thresholds. Statistical testing and model building resulted in a peak profiling model of five relevant peaks with 88% overall sensitivity and 91% specificity, and overall correctness of 90%. High-resolution MS of 40 samples in the 2-10 kDa range resulted in 646 identified proteins, and pattern matching identified four of the five model peaks within significant parameters, namely programmed cell death 6 interacting protein (PDCD6IP/Alix/AIP1), Rabenosyn-5 (ZFYVE20), protein S100A8, and protein S100A9, of which the first two were validated by Western blotting.
  
  
  CONCLUSIONS
  We demonstrate that MS analysis of human urine can identify lead biomarker candidates in uGI cancers, which makes this technique potentially useful in defining and consolidating biomarker patterns for uGI cancer screening.
authors: Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.|School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors: Holger
authors: H
authors: Husi
authors: School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors: Richard J E
authors: RJ
authors: Skipworth
authors: School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors: Andrew
authors: A
authors: Cronshaw
authors: School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors: Nathan A
authors: NA
authors: Stephens
authors: School of Medical Sciences, University of Aberdeen, Aberdeen, UK.
authors: Henning
authors: H
authors: Wackerhage
authors: School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.|School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
authors: Carolyn
authors: C
authors: Greig
authors: School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors: Kenneth C H
authors: KC
authors: Fearon
authors: School of Clinical Sciences, University of Edinburgh, Edinburgh, UK.
authors: James A
authors: JA
authors: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000302:isolation & purification / Q000652:urine*; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000652:urine*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000652:urine*; D002846:Chromatography, Affinity; D056827:Endosomal Sorting Complexes Required for Transport / Q000302:isolation & purification / Q000652:urine*; D004938:Esophageal Neoplasms / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000652:urine*; D033921:Vesicular Transport Proteins / Q000302:isolation & purification / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human; C416362:RBSN protein, human; D033921:Vesicular Transport Proteins
keywords: Mass spectrometry; Upper gastrointestinal cancer; Urine biomarker