title: Urinary levels of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein as a diagnostic biomarker in patients with bladder cancer.
abstract: BACKGROUND
  To assess the possibility of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) as a biological marker for detecting Bladder cancer (BCa), we examined the expression of HIP/PAP in both BCa specimens and BCa cell lines and measured HIP/PAP levels in urine from patients with BCa.
  
  
  METHODS
  HIP/PAP expression in BCa samples was evaluated by western blot analysis, and urinary levels of HIP/PAP in patients with BCa were measured by enzyme-linked immunosorbent assay. Urine samples were collected from 10 healthy volunteers and 109 with benign urological disorders as controls, and from 101 patients who were diagnosed with BCa.
  
  
  RESULTS
  HIP/PAP was highly expressed in BCa samples as compared with control bladder. Urinary HIP/PAP concentrations were significantly higher in BCa patients than in controls (median value; 3.184 pg/mL vs. 55.200 pg/mL, P <0.0001, by Mann-Whitney U test). Urinary HIP/PAP levels in BCa patients correlated positively with pathological T stages and progression-risk groups among non-muscle invasive BCa (P = 0.0008, by Kruskal-Wallis test). Regarding the recurrence-risk classifications of non-muscle invasive BCa, the urinary levels of HIP/PAP were significantly higher in the intermediate than in the low risk group (P = 0.0002, by Mann-Whitney U test). Based on a cut-off of 8.5 pg/mL, the ability of urinary HIP/PAP levels to detect BCa had a sensitivity of 80.2%, specificity of 78.2%, positive predictive value (PPV) of 75.7%, and negative predictive value (NPV) of 82.3%.
  
  
  CONCLUSIONS
  HIP/PAP was abundantly expressed in BCa, and the urinary levels of HIP/PAP could be a novel and potent biomarker for detection of BCa, and also for predicting the risks of recurrence- and progression-risk of non-muscle invasive BCa. A large scale study will be needed to establish the usefulness of this biomarker.
authors.affiliation: Department of Urology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Nitta
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Makino
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kawashima
authors.forename: Juan L
authors.initials: JL
authors.lastname: Iovanna
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D000073718:Pancreatitis-Associated Proteins; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human