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Logo of bmcurolBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Urology
 
BMC Urol. 2012; 12: 24.
Published online Sep 4, 2012. doi:  10.1186/1471-2490-12-24
PMCID: PMC3487857
Urinary levels of Hepatocarcinoma-intestine-pancreas/Pancreatitis-associated protein as a diagnostic biomarker in patients with bladder cancer
Yujiro Nitta,1 Hiroyuki Konishi,2 Tetsuya Makino,1 Tomoaki Tanaka,1 Hidenori Kawashima,1 Juan L Iovanna,3 Tatsuya Nakatani,1 and Hiroshi Kiyamacorresponding author2
1Department of Urology, Graduate School of Medicine, Osaka City University, Osaka, Japan
2Department of Functional Anatomy and Neuroscience, Graduate School of Medicine, Nagoya University, Nagoya, Japan
3INSERM U.624, Stress Cellulaire, France
corresponding authorCorresponding author.
Yujiro Nitta: m1159425/at/med.osaka-cu.ac.jp; Hiroyuki Konishi: konishi/at/nagoya-u.ac.jp; Tetsuya Makino: makino/at/med.osaka-cu.ac.jp; Tomoaki Tanaka: tomoaki826/at/msic.med.osaka-cu.ac.jp; Hidenori Kawashima: hidenori/at/msic.med.osaka-cu.ac.jp; Juan L Iovanna: juan.iovanna/at/inserm.fr; Tatsuya Nakatani: nakatani/at/med.osaka-cu.ac.jp; Hiroshi Kiyama: kiyama/at/med.nagoya-u.ac.jp
Received May 2, 2012; Accepted August 31, 2012.
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.
Keywords: Bladder cancer, Urinary marker, HIP/PAP, ELISA, ROC
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