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Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer

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Abstract

Purpose

Sphingolipids are bioactive lipids implicated in apoptosis, cell survival and proliferation. We analyzed the prognostic value of enzymes from sphingolipid metabolism in breast cancer.

Methods

Differences in expression of ceramide galactosyl transferase (UGT8), ceramide kinase (CERK), and Ganglioside GD3-Synthase (ST8SIA1) in breast cancer cells were investigated by using microarray data of 1,581 tumor samples.

Results

UGT8, CERK, and ST8SIA1 were associated with poor pathohistological grading (P < 0.001). High CERK expression was correlated with ErbB2 status (P = 0.006). Among ER positive breast cancers a significant worse prognosis for patients with tumors showing low ST8SIA1 and UGT8 expression was observed. In the ER negative subgroup those samples with high CERK expression displayed a worse prognosis. In a multivariate analysis only ST8SIA1 and tumor size remained significant.

Conclusions

Our experiments reveal that expression of enzymes from the sphingolipid metabolism has prognostic implications in breast cancer.

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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. Tissue samples of breast cancer cases of the University of Frankfurt were obtained with informed consent and approval of the institutional review board of the University of Frankfurt.

Conflict of interest statement

There are no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany

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

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

    Dirk Metzler

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  1. Eugen Ruckhäberle
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Correspondence to Eugen Ruckhäberle.

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E. Ruckhäberle and T. Karn contributed equally to this manuscript.

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Ruckhäberle, E., Karn, T., Rody, A. et al. Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer. J Cancer Res Clin Oncol 135, 1005–1013 (2009). https://doi.org/10.1007/s00432-008-0536-6

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