Low circulating serum levels of second mitochondria-derived activator             of caspase (Smac/DIABLO) in patients with bladder cancer.
Smac/DIABLO promotes apoptosis by antagonizing inhibitor of apoptosis proteins.             The expression of Smac/DIABLO in tissues has been reported in various cancers;             however, little is known about circulating levels of Smac/DIABLO. The present             study was designed to first determine if Smac/DIABLO can be detected in the serum             and then assess whether the circulating levels of Smac/DIABLO are of prognostic             significance in patients with bladder cancer. The levels of Smac/DIABLO in the             sera of 173 patients with bladder cancer and 36 normal donors were determined             by using an enzyme-linked immunosorbent assay. The mean serum level of Smac/DIABLO             in patients with bladder cancer was approximately 2-fold lower than that in normal             donors. The mean level of serum Smac/DIABLO in patients with muscle-invasive bladder             cancer was lower than that in patients with non-muscle invasive cancer. In addition,             the mean serum Smac/DIABLO level in patients with T4 muscle-invasive bladder cancer             was lower than that in patients with T2 and T3 cancers. The mean serum level of             Smac/DIABLO in patients with Grade 3 bladder cancer was lower than that in patients             with Grade 1 and Grade 2 cancers. Analysis by Kaplan-Meier revealed that patients             with Ta and T1 non-muscle invasive bladder cancer with high level of serum Smac/DIABLO             (more than mean value) had a longer post-operative tumor-free interval than those             with low level (less than mean value) in the 3-year follow-up. Furthermore, patients             with T2-T4 muscle-invasive bladder cancer with high serum Smac/DIABLO level (more             than mean value) had a higher post-operative disease-free rate when compared with             patients with low level (less than mean value) in the 5-year follow-up. The present             study is the first to analyze circulating levels of Smac/DIABLO in the serum.             The findings demonstrate that the mean serum level of Smac/DIABLO was downregulated             in patients with bladder cancer compared to control healthy individuals, especially             high grade muscle-invasive bladder cancer. Noteworthy, lower serum level of Smac/DIABLO             predicted early recurrence in patients with bladder cancer. Overall, the findings             suggest that measuring the levels of Smac/DIABLO in the serum may be considered             a prognostic parameter in patients with bladder cancer. Furthermore, Smac/DIABLO             may be a molecular therapeutic target in bladder cancer.
Department of Urology, Faculty of Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan. uro046@poh.osaka-med.ac.jp
Yoichi
Y
Mizutani
Yoji
Y
Katsuoka
Benjamin
B
Bonavida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000097:blood*; D018572:Disease-Free Survival; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood* / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000097:blood* / Q000172:deficiency; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins