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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 presentstudy was designed to first determine if Smac/DIABLO can be detected in the serumand then assess whether the circulating levels of Smac/DIABLO are of prognosticsignificance in patients with bladder cancer. The levels of Smac/DIABLO in thesera of 173 patients with bladder cancer and 36 normal donors were determinedby using an enzyme-linked immunosorbent assay. The mean serum level of Smac/DIABLOin patients with bladder cancer was approximately 2-fold lower than that in normaldonors. The mean level of serum Smac/DIABLO in patients with muscle-invasive bladdercancer 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 cancerwas lower than that in patients with T2 and T3 cancers. The mean serum level ofSmac/DIABLO in patients with Grade 3 bladder cancer was lower than that in patientswith Grade 1 and Grade 2 cancers. Analysis by Kaplan-Meier revealed that patientswith 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 thosewith low level (less than mean value) in the 3-year follow-up. Furthermore, patientswith T2-T4 muscle-invasive bladder cancer with high serum Smac/DIABLO level (morethan mean value) had a higher post-operative disease-free rate when compared withpatients with low level (less than mean value) in the 5-year follow-up. The presentstudy 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 downregulatedin patients with bladder cancer compared to control healthy individuals, especiallyhigh grade muscle-invasive bladder cancer. Noteworthy, lower serum level of Smac/DIABLOpredicted early recurrence in patients with bladder cancer. Overall, the findingssuggest that measuring the levels of Smac/DIABLO in the serum may be considereda prognostic parameter in patients with bladder cancer. Furthermore, Smac/DIABLOmay be a molecular therapeutic target in bladder cancer.

Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer