Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer

Fong, M.Y.; McDunn, J.; Kakar, S.S. (2011) Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer. Plos One, 6 (5). p. 12. ISSN 1932-6203

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Abstract

In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and beta-oxidation of fatty acids-such as carnitine (1.79 fold in EOC, p < 0.001; 1.88 fold in MOC, p < 0.001), acetylcarnitine (1.75 fold in EOC, p < 0.001; 2.39 fold in MOC, p < 0.001), and butyrylcarnitine (3.62 fold, p < 0.0094 in EOC; 7.88 fold, p < 0.001 in MOC). There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098) and phenyllactate (195.45 fold; p < 0.0023) in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316) and in MOC (2.25 fold, p < 0.001) and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.

Item Type: Article
Creators:
  1. Fong, M.Y.(Department of Parasitology, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA)
  2. McDunn, J.
  3. Kakar, S.S.
Journal or Publication Title: Plos One
Additional Information: ISI Document Delivery No.: 766HI Times Cited: 1 Cited Reference Count: 94 Fong, Miranda Y. McDunn, Jonathan Kakar, Sham S.
Uncontrolled Keywords: Magnetic-Resonance-Spectroscopy Tandem Mass-Spectrometry Human Colorectal-Cancer N-Acetylaspartate Breast-Cancer Prostate-Cancer Aerobic Glycolysis Vitamin-E Cells Taurine
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Fong Mun Yik
Date Deposited: 13 Jun 2012 09:29
Last Modified: 13 Jun 2012 09:29
URI: http://eprints.um.edu.my/id/eprint/3279

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