Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer.
OBJECTIVE
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.
Department of Gynecology, J. W. Goethe-University, Frankfurt, Germany.
Eugen
E
Ruckhäberle
Thomas
T
Karn
Lars
L
Hanker
Regine
R
Gätje
Dirk
D
Metzler
Uwe
U
Holtrich
Manfred
M
Kaufmann
Achim
A
Rody
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D018275:Carcinoma, Lobular / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D049109:Cell Proliferation; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D005964:Glucosyltransferases; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C023246:ceramide glucosyltransferase