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

Eugen Ruckhäberle; Thomas Karn; Lars Hanker; Regine Gätje; Dirk Metzler; Uwe Holtrich; Manfred Kaufmann; Achim Rody

doi:10.1007/s00432-008-0436-9

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

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

Klinik für Frauenheilkunde und Geburtshilfe

Johann Wolfgang Goethe-Universität

33 Zitate (Scopus)

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.

Originalsprache	Englisch
Zeitschrift	Journal of Cancer Research and Clinical Oncology
Jahrgang	135
Ausgabenummer	1
Seiten (von - bis)	81-90
Seitenumfang	10
ISSN	0171-5216
DOIs	https://doi.org/10.1007/s00432-008-0436-9
Publikationsstatus	Veröffentlicht - 01.2009

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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 PXeger-Stiftung, Bamberg, and the BANSS-Stiftung, Biedenkopf.

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10.1007/s00432-008-0436-9

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title = "Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer",

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.",

author = "Eugen Ruckh{\"a}berle and Thomas Karn and Lars Hanker and Regine G{\"a}tje and Dirk Metzler and Uwe Holtrich and Manfred Kaufmann and Achim Rody",

note = "Funding Information: 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 PXeger-Stiftung, Bamberg, and the BANSS-Stiftung, Biedenkopf.",

year = "2009",

month = jan,

doi = "10.1007/s00432-008-0436-9",

language = "English",

volume = "135",

pages = "81--90",

journal = "Journal of Cancer Research and Clinical Oncology",

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publisher = "Springer Science and Business Media Deutschland GmbH",

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T1 - Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer

AU - Ruckhäberle, Eugen

AU - Karn, Thomas

AU - Hanker, Lars

AU - Gätje, Regine

AU - Metzler, Dirk

AU - Holtrich, Uwe

AU - Kaufmann, Manfred

AU - Rody, Achim

N1 - Funding Information: 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 PXeger-Stiftung, Bamberg, and the BANSS-Stiftung, Biedenkopf.

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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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U2 - 10.1007/s00432-008-0436-9

DO - 10.1007/s00432-008-0436-9

M3 - Journal articles

C2 - 18560890

AN - SCOPUS:56649099155

SN - 0171-5216

VL - 135

SP - 81

EP - 90

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

IS - 1

ER -

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

Abstract

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