TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=56649099155&partnerID=8YFLogxK
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 -