Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer.
OBJECTIVE
Sphingolipids are bioactive lipids implicated in apoptosis, cell survival and proliferation. We analyzed the prognostic value of enzymes from sphingolipid metabolism in breast cancer.


METHODS
Differences in expression of ceramide galactosyl transferase (UGT8), ceramide kinase (CERK), and Ganglioside GD3-Synthase (ST8SIA1) in breast cancer cells were investigated by using microarray data of 1,581 tumor samples.


RESULTS
UGT8, CERK, and ST8SIA1 were associated with poor pathohistological grading (P < 0.001). High CERK expression was correlated with ErbB2 status (P = 0.006). Among ER positive breast cancers a significant worse prognosis for patients with tumors showing low ST8SIA1 and UGT8 expression was observed. In the ER negative subgroup those samples with high CERK expression displayed a worse prognosis. In a multivariate analysis only ST8SIA1 and tumor size remained significant.


CONCLUSIONS
Our experiments reveal that expression of enzymes from the sphingolipid metabolism has prognostic implications in breast cancer.
Ruckhäberle
Eugen
E
Department of Obstetrics and Gynecology, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. eugen.ruckhaeberle@med.uni-frankfurt.de
Karn
Thomas
T
Rody
Achim
A
Hanker
Lars
L
Gätje
Regine
R
Metzler
Dirk
D
Holtrich
Uwe
U
Kaufmann
Manfred
M
D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D051147:Ganglioside Galactosyltransferase / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
D051147:Ganglioside Galactosyltransferase; D017853:Phosphotransferases (Alcohol Group Acceptor); D018719:Erb-b2 Receptor Tyrosine Kinases; D012799:Sialyltransferases; C511211:UGT8 protein, human; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase; C066324:ceramide kinase