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Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer

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Abstract

Purpose

Multidrug resistance (MDR) has been linked to sphingolipid metabolism and preclinical data ascribe glucosylceramide synthase (GCS) a major role for MDR especially in breast cancer cells but no profound data are available on the expression of this potential therapeutic target in clinical breast cancer specimens.

Methods

We analyzed microarray data of GCS expression in a large cohort of 1,681 breast tumors.

Results

Expression of GCS was associated with a positive estrogen receptor (ER) status, lower histological grading, low Ki67 levels and ErbB2 negativity (P < 0.001 for all). In univariate analysis there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression but this significance was lost in multivariate Cox regression.

Conclusions

Our results suggest ER positive tumors may be the most promising candidates for a potential therapeutic application of GCS inhibitors.

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Acknowledgments

We thank Samira Adel and Katherina Kourtis for expert technical assistance. This work was supported by grants from the Deutsche Krebshilfe, the Margarete Bonifer-Stiftung, Bad Soden, the Dr. Robert Pfleger-Stiftung, Bamberg, and the BANSS-Stiftung, Biedenkopf.

Conflicts of interest statement

There are no conflicts of interest to declare.

Role of the funding source

The funding sources were not involved in the study design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

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Ethical approval was not required.

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Authors and Affiliations

  1. Department of Gynecology, J. W. Goethe-University, Frankfurt, Germany

    Eugen Ruckhäberle, Thomas Karn, Lars Hanker, Regine Gätje, Uwe Holtrich, Manfred Kaufmann & Achim Rody

  2. Department of Computer Science and Mathematics, J. W. Goethe-University, Frankfurt, Germany

    Dirk Metzler

Authors
  1. Eugen Ruckhäberle
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  2. Thomas Karn
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  3. Lars Hanker
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  4. Regine Gätje
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  6. Uwe Holtrich
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  7. Manfred Kaufmann
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  8. Achim Rody
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Corresponding author

Correspondence to Thomas Karn.

Additional information

Eugen Ruckhäberle and Thomas Karn contributed equally to this work.

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Ruckhäberle, E., Karn, T., Hanker, L. et al. Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer. J Cancer Res Clin Oncol 135, 81–90 (2009). https://doi.org/10.1007/s00432-008-0436-9

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  • DOI: https://doi.org/10.1007/s00432-008-0436-9

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