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

S. F. Brockmöller, Elmar Bucher, B. M. Müller, J. Budczies, Mika Hilvo, J. Leether Griffin, Matej Oresic, Olli Kallioniemi, Kristiina Iljin, S. Loibl, S. Darb-Esfahani, B. V. Sinn, F. Klauschen, J. Prinzler, N. Bangemann, F. Ismaeel, O. Fiehn, M. Dietel, C. Denkert (Corresponding Author)

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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
Pages (from-to)850-860
Number of pages11
JournalJournal of Proteome Research
Volume11
Issue number2
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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Acyltransferases
Metabolomics
Phospholipids
Hormones
Breast Neoplasms
Survival
Messenger RNA
Proteins
Biosynthesis
Phosphatidylcholines
Metabolism
Tumors
Triglycerides
Lipid Metabolism
Computer Simulation
Tissue
Membranes
Lipids
Neoplasms
Breast

Keywords

  • breast cancer
  • metabolomic profile
  • lipidomic profile

Cite this

Brockmöller, S. F. ; Bucher, Elmar ; Müller, B. M. ; Budczies, J. ; Hilvo, Mika ; Leether Griffin, J. ; Oresic, Matej ; Kallioniemi, Olli ; Iljin, Kristiina ; Loibl, S. ; Darb-Esfahani, S. ; Sinn, B. V. ; Klauschen, F. ; Prinzler, J. ; Bangemann, N. ; Ismaeel, F. ; Fiehn, O. ; Dietel, M. ; Denkert, C. / Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer : Link to patient survival, hormone receptor status and metabolic profiling. In: Journal of Proteome Research. 2012 ; Vol. 11, No. 2. pp. 850-860.
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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.",
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author = "Brockm{\"o}ller, {S. F.} and Elmar Bucher and M{\"u}ller, {B. M.} and J. Budczies and Mika Hilvo and {Leether Griffin}, J. and Matej Oresic and Olli Kallioniemi and Kristiina Iljin and S. Loibl and S. Darb-Esfahani and Sinn, {B. V.} and F. Klauschen and J. Prinzler and N. Bangemann and F. Ismaeel and O. Fiehn and M. Dietel and C. Denkert",
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Brockmöller, SF, Bucher, E, Müller, BM, Budczies, J, Hilvo, M, Leether Griffin, J, Oresic, M, Kallioniemi, O, Iljin, K, Loibl, S, Darb-Esfahani, S, Sinn, BV, 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, vol. 11, no. 2, pp. 850-860. https://doi.org/10.1021/pr200685r

Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer : Link to patient survival, hormone receptor status and metabolic profiling. / Brockmöller, S. F.; Bucher, Elmar; Müller, B. M.; Budczies, J.; Hilvo, Mika; Leether Griffin, J.; Oresic, Matej; Kallioniemi, Olli; Iljin, Kristiina; Loibl, S.; Darb-Esfahani, S.; Sinn, B. V.; Klauschen, F.; Prinzler, J.; Bangemann, N.; Ismaeel, F.; Fiehn, O.; Dietel, M.; Denkert, C. (Corresponding Author).

In: Journal of Proteome Research, Vol. 11, No. 2, 2012, p. 850-860.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer

T2 - Link to patient survival, hormone receptor status and metabolic profiling

AU - Brockmöller, S. F.

AU - Bucher, Elmar

AU - Müller, B. M.

AU - Budczies, J.

AU - Hilvo, Mika

AU - Leether Griffin, J.

AU - Oresic, Matej

AU - Kallioniemi, Olli

AU - Iljin, Kristiina

AU - Loibl, S.

AU - Darb-Esfahani, S.

AU - Sinn, B. V.

AU - Klauschen, F.

AU - Prinzler, J.

AU - Bangemann, N.

AU - Ismaeel, F.

AU - Fiehn, O.

AU - Dietel, M.

AU - Denkert, C.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - breast cancer

KW - metabolomic profile

KW - lipidomic profile

U2 - 10.1021/pr200685r

DO - 10.1021/pr200685r

M3 - Article

VL - 11

SP - 850

EP - 860

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 2

ER -