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

J Cancer Res Clin Oncol. 2009 Aug;135(8):1005-13. doi: 10.1007/s00432-008-0536-6. Epub 2009 Jan 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics
  • Disease-Free Survival
  • Female
  • Ganglioside Galactosyltransferase / genetics*
  • Ganglioside Galactosyltransferase / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism
  • Tissue Array Analysis

Substances

  • UGT8 protein, human
  • Ganglioside Galactosyltransferase
  • Sialyltransferases
  • alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
  • Phosphotransferases (Alcohol Group Acceptor)
  • ceramide kinase
  • Receptor, ErbB-2