Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling

Scarlet F. Brockmöller, Elmar Bucher, Berit M. Müller, Jan Budczies, Mika Hilvo, Julian L. Griffin, Matej Orešič, Olli Kallioniemi, Kristiina Iljin, Sibylle Loibl, Silvia Darb-Esfahani, Bruno V. Sinn, Frederick Klauschen, Judith Prinzler, Nikola Bangemann, Fakher Ismaeel, Oliver Fiehn, Manfred Dietel, Carsten Denkert

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)850-860
Number of pages11
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
StatePublished - Feb 3 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Brockmöller, S. F., Bucher, E., Müller, B. M., Budczies, J., Hilvo, M., Griffin, J. L., Orešič, M., Kallioniemi, O., Iljin, K., Loibl, S., Darb-Esfahani, S., Sinn, B. V., Klauschen, F., Prinzler, J., Bangemann, N., Ismaeel, F., Fiehn, O., Dietel, M., & Denkert, C. (2012). Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling. Journal of Proteome Research, 11(2), 850-860. https://doi.org/10.1021/pr200685r