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

doi: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

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

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	850-860
Number of pages	10
Journal	Journal of Proteome Research
Volume	11
Issue number	2
DOIs	https://doi.org/10.1021/pr200685r https://doi.org/10.1021/acs.jproteome.2c00181
Publication status	Published - 9 Nov 2011

Bibliographical note

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.

Keywords

breast cancer
metabolomic profile
lipidomic profile

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. (2011). 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, https://doi.org/10.1021/acs.jproteome.2c00181

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, Scarlet F; Bucher, Elmar; Müller, Berit M et al.
In: Journal of Proteome Research, Vol. 11, No. 2, 09.11.2011, p. 850-860.

Research output: Contribution to journal › Article › peer-review

Brockmöller, SF, Bucher, E, Müller, BM, Budczies, J, Hilvo, M, Griffin, JL, Orešič, 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 2011, '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, https://doi.org/10.1021/acs.jproteome.2c00181

Brockmöller SF, Bucher E, Müller BM, Budczies J, Hilvo M, Griffin JL et al. 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. 2011 Nov 9;11(2):850-860. doi: 10.1021/pr200685r, 10.1021/acs.jproteome.2c00181

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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.",

keywords = "breast cancer, metabolomic profile, lipidomic profile",

author = "Brockm{\"o}ller, {Scarlet F} and Elmar Bucher and M{\"u}ller, {Berit M} and Jan Budczies and Mika Hilvo and Griffin, {Julian L} and Matej Ore{\v s}i{\v c} and Olli Kallioniemi and Kristiina Iljin and Sibylle Loibl and Silvia Darb-Esfahani and Sinn, {Bruno V} and Frederick Klauschen and Judith Prinzler and Nikola Bangemann and Fakher Ismaeel and Oliver Fiehn and Manfred Dietel and Carsten Denkert",

note = "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.",

year = "2011",

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doi = "10.1021/pr200685r",

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T1 - Integration of Metabolomics and Expression of Glycerol-3-phosphate Acyltransferase (GPAM) in Breast Cancer─Link to Patient Survival, Hormone Receptor Status, and Metabolic Profiling

AU - Brockmöller, Scarlet F

AU - Bucher, Elmar

AU - Müller, Berit M

AU - Budczies, Jan

AU - Hilvo, Mika

AU - Griffin, Julian L

AU - Orešič, Matej

AU - Kallioniemi, Olli

AU - Iljin, Kristiina

AU - Loibl, Sibylle

AU - Darb-Esfahani, Silvia

AU - Sinn, Bruno V

AU - Klauschen, Frederick

AU - Prinzler, Judith

AU - Bangemann, Nikola

AU - Ismaeel, Fakher

AU - Fiehn, Oliver

AU - Dietel, Manfred

AU - Denkert, Carsten

N1 - 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.

PY - 2011/11/9

Y1 - 2011/11/9

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

C2 - 35642679

SN - 1535-3893

VL - 11

SP - 850

EP - 860

JO - Journal of Proteome Research

JF - Journal of Proteome Research

IS - 2

ER -

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

Bibliographical note

Keywords

UN SDGs

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