Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer
Ruckhäberle, E.; Karn, T.; Rody, A.; Hanker, L.; Gätje, R.; Metzler, D.; Holtrich, U.; Kaufmann, M.
Journal of Cancer Research and Clinical Oncology 135(8): 1005-1013
Sphingolipids are bioactive lipids implicated in apoptosis, cell survival and proliferation. We analyzed the prognostic value of enzymes from sphingolipid metabolism in breast cancer. 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. 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. Our experiments reveal that expression of enzymes from the sphingolipid metabolism has prognostic implications in breast cancer.