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Expression levels of the mitochondrial IAP antagonists Smac/DIABLO and Omi/HtrA2 in clear-cell renal cell carcinomas and their prognostic value

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Numerous molecular parameters are thought to be implicated in renal cell carcinoma (RCC) tumor biology and may therefore reflect the malignant potential of individual tumors. Their investigation may thus help to improve the postoperative management of RCC patients. This study characterized the mRNA expression levels and evaluated the prognostic effect of the mitochondrial inhibitor of apoptosis antagonists Smac/DIABLO and Omi/HtrA2 in tumor tissue from clear-cell RCC patients.

Methods

The relative gene expression (RGE) was analyzed by real-time RT-PCR in tumor tissue obtained from 85 patients (median follow-up: 47 months) following surgical treatment. Expression data was correlated to clinico-pathological variables and outcome.

Results

The RGE of Smac/DIABLO was lowest in patients with primary metastases, intermediate in those who progressed to metastatic disease, and highest in those who did not develop metastases during follow-up (P = 0.006). Expression levels of Smac/DIABLO and Omi/HtrA2 were strongly correlated with each other (Pearson coefficient 0.90). Recurrence-free and tumor-specific survival was shorter in patients with low Smac/DIABLO levels (P = 0.019 and P = 0.001) as well as in those with low Omi/HtrA2 tumor expression (P = 0.033 and P = 0.032). Contrary to Omi/HtrA2, low Smac/DIABLO levels were still predictive of a reduced time to recurrence (hazard rate 5.31; 95% CI: 1.16–24.21) and tumor-specific survival (hazard rate 4.24; 95% CI: 1.22–14.77) in explorative multivariate analysis.

Conclusions

The mRNA expression levels of the mitochondrial IAP antagonists Smac/DIABLO and Omi/HtrA2 are strongly inter-correlated, but do not relate to tumor stage or grade of RCC. Our data suggest that expression of Smac/DIABLO, but not Omi/HtrA2, is inversely associated with outcome of RCC patients.

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Acknowledgments

The authors wish to thank Ms. Petra von Kwiatkowski, Ms. Waltraud Jekabsons and Ms. Antonia Maass from the Department of Urology for their excellent support in assessing and preparing the samples.

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Authors and Affiliations

  1. Department of Urology, Charité––Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Carsten Kempkensteffen, Stefan Hinz, Frank Christoph, Hans Krause, Mark Schrader, Martin Schostak, Kurt Miller & Steffen Weikert

  2. Department of Urology, Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue A3-East, Baltimore, MD, 21224, USA

    Ahmed Magheli

Authors
  1. Carsten Kempkensteffen
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  2. Stefan Hinz
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  3. Frank Christoph
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  4. Hans Krause
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  5. Ahmed Magheli
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  6. Mark Schrader
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  7. Martin Schostak
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  8. Kurt Miller
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  9. Steffen Weikert
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Correspondence to Carsten Kempkensteffen.

Additional information

The grant sponsor of the study was: Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin.

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Kempkensteffen, C., Hinz, S., Christoph, F. et al. Expression levels of the mitochondrial IAP antagonists Smac/DIABLO and Omi/HtrA2 in clear-cell renal cell carcinomas and their prognostic value. J Cancer Res Clin Oncol 134, 543–550 (2008). https://doi.org/10.1007/s00432-007-0317-7

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  • DOI: https://doi.org/10.1007/s00432-007-0317-7

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