title: Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling.
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.
authors: Institute of Pathology, Charité- Universitätsmedizin Berlin , 10117 Berlin, Germany.
authors: Scarlet F
authors: SF
authors: Brockmöller
authors: Elmar
authors: E
authors: Bucher
authors: Berit M
authors: BM
authors: Müller
authors: Jan
authors: J
authors: Budczies
authors: Mika
authors: M
authors: Hilvo
authors: Julian L
authors: JL
authors: Griffin
authors: Matej
authors: M
authors: Orešič
authors: Olli
authors: O
authors: Kallioniemi
authors: Kristiina
authors: K
authors: Iljin
authors: Sibylle
authors: S
authors: Loibl
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Bruno V
authors: BV
authors: Sinn
authors: Frederick
authors: F
authors: Klauschen
authors: Judith
authors: J
authors: Prinzler
authors: Nikola
authors: N
authors: Bangemann
authors: Fakher
authors: F
authors: Ismaeel
authors: Oliver
authors: O
authors: Fiehn
authors: Manfred
authors: M
authors: Dietel
authors: Carsten
authors: C
authors: Denkert
mesh_terms: D001940:Breast / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D050356:Lipid Metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D005992:Glycerol-3-Phosphate O-Acyltransferase; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen