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

  • Authors:
    • Yoichi Mizutani
    • Yoji Katsuoka
    • Benjamin Bonavida
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  • Published online on: January 3, 2012     https://doi.org/10.3892/ijo.2012.1324
  • Pages: 1246-1250
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Abstract

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 post­operative 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 post­operative 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.
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April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Mizutani Y, Katsuoka Y and Bonavida B: Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer. Int J Oncol 40: 1246-1250, 2012
APA
Mizutani, Y., Katsuoka, Y., & Bonavida, B. (2012). Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer. International Journal of Oncology, 40, 1246-1250. https://doi.org/10.3892/ijo.2012.1324
MLA
Mizutani, Y., Katsuoka, Y., Bonavida, B."Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer". International Journal of Oncology 40.4 (2012): 1246-1250.
Chicago
Mizutani, Y., Katsuoka, Y., Bonavida, B."Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer". International Journal of Oncology 40, no. 4 (2012): 1246-1250. https://doi.org/10.3892/ijo.2012.1324