Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer

Purpose: 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.