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

28 Citations (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.

Original languageEnglish
JournalJournal of Cancer Research and Clinical Oncology
Volume135
Issue number1
Pages (from-to)81-90
Number of pages10
ISSN0171-5216
DOIs
Publication statusPublished - 01.2009

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