Acid ceramidase 1 expression correlates with a better prognosis in ER-positive breast cancer.
OBJECTIVE
Ceramide and sphingosine mediate response to cancer therapy, inhibit cell growth and induce apoptosis in vitro. Only a few clinical data about the impact of ceramide and sphingosine iny vivo are available. We investigated the relevance of ceramide- and sphingosine-generating enzymes in breast cancer (acid ceramidase 1 (ASAH1), ceramide synthases 4 (LASS4) and 6 (LASS6)) by means of gene expression analysis.


METHODS
We analyzed differences in ASAH1, LASS4 and LASS6 on mRNA level between breast cancer subgroups using microarray data from 1581 tumor samples.


RESULTS
High ASAH1, LASS4 and LASS6 expression correlates with pathohistological grading (p < 0.001) and estrogen receptor (ER) status (p < 0.001). High ASAH1 expression was associated with a larger tumor size >2 cm (p = 0.003), while high LASS6 expression was correlated with ErbB2 negativity (p < 0.001). In survival analysis, we detected a significant better prognosis of patients with higher ASAH1 expression (p = 0.002) in the ER-positive subgroup. In contrast, expression of LASS4 or LASS6 did not show any prognostic impact. In the multivariate analysis, only ASAH1 expression (p = 0.002), tumor size (p < 0.0001) and ErbB2 positivity (p = 0.041) remained significant.


CONCLUSIONS
ASAH1 is an estrogen-dependent member of the sphingolipid metabolism, which might provide further prognostic information in ER-positive breast cancers.
Ruckhäberle
E
E
Departments of Obstetrics and Gynecology, J.W.Goethe-University, Frankfurt, Germany.
Holtrich
U
U
Engels
K
K
Hanker
L
L
Gätje
R
R
Metzler
D
D
Karn
T
T
Kaufmann
M
M
Rody
A
A
D055573:Acid Ceramidase / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010088:Oxidoreductases / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D013107:Sphingolipids / Q000378:metabolism
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013107:Sphingolipids; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; C526693:ASAH1 protein, human; D055573:Acid Ceramidase