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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Aged
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Aged, 80 and over
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Breast Neoplasms / enzymology*
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology
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Carcinoma, Ductal, Breast / enzymology*
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Carcinoma, Ductal, Breast / genetics
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Carcinoma, Ductal, Breast / secondary
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Carcinoma, Lobular / enzymology*
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Carcinoma, Lobular / genetics
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Carcinoma, Lobular / secondary
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Cell Proliferation
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Child
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Female
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Gene Expression Profiling
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Glucosyltransferases / genetics
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Glucosyltransferases / metabolism*
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Humans
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Ki-67 Antigen / genetics
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Ki-67 Antigen / metabolism
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Middle Aged
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Oligonucleotide Array Sequence Analysis
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Prognosis
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / metabolism
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism
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Survival Rate
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Young Adult
Substances
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Biomarkers, Tumor
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Ki-67 Antigen
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Receptors, Estrogen
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Glucosyltransferases
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ceramide glucosyltransferase
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Receptor, ErbB-2