Abstract
BackgroundTo 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.MethodsHIP/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.ResultsHIP/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%.ConclusionsHIP/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.
Highlights
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
We previously reported that the interstitial cystitis (IC) induced expression of some regenerating isletderived (Reg) family members in Cyclophosphamide-induced cystitis model of rat, and demonstrated that PAP-III (Reg-IIIγ in humans) was expressed in the urothelium of the bladder and, on the other hand, that PAP-I (HIP/PAP in humans) was expressed in primary afferent neurons of dorsal root ganglia that innervate the bladder
HIP/PAP expression in the BCa specimens and BCa cell lines As shown in Figure 1A, western blot analysis using the anti-HIP/PAP antibody revealed that the expression of HIP/PAP protein was detectable in BCa samples
Summary
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. Urothelial carcinoma is the most common Bladder cancer (BCa). [4] To date, several Reg family proteins have been identified and described under various nomenclatures such as pancreatitis-associated protein (PAP) and hepatocarcinoma-intestine-pancreas (HIP). They are broadly categorized into four groups, namely, type I to IV. We evaluated the diagnostic accuracy of urinary HIP/PAP as compared with conventional markers, such as urinary NMP22 and BTA
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