Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.
Correction to "Integration of Metabolomics and Expression of Glycerol-3-phosphate Acyltransferase (GPAM) in Breast Cancer─Link to Patient Survival, Hormone Receptor Status, and Metabolic Profiling" The authors regret that in the original publication Figure 2D and Figure 4B were incorrectly presented.
Acknowledgement: We would like to thank Petra Wachs, Britta Beyer, and Ulla Lahtinen for their excellent technical assistance. This work was supported by the METAcancer project of the EU 7th Framework Programme. The costs of publication of this article were defrayed as part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- breast cancer
- metabolomic profile
- lipidomic profile