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

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...

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Autores principales:	Miranda Y Fong, Jonathan McDunn, Sham S Kakar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b54d5cf51ebf477bab841a9a57f9f31d
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spelling	oai:doaj.org-article:b54d5cf51ebf477bab841a9a57f9f31d2021-11-18T06:53:41ZIdentification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.1932-620310.1371/journal.pone.0019963https://doaj.org/article/b54d5cf51ebf477bab841a9a57f9f31d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625518/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In 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 β-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.Miranda Y FongJonathan McDunnSham S KakarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19963 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Miranda Y Fong Jonathan McDunn Sham S Kakar Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
description	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 β-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.
format	article
author	Miranda Y Fong Jonathan McDunn Sham S Kakar
author_facet	Miranda Y Fong Jonathan McDunn Sham S Kakar
author_sort	Miranda Y Fong
title	Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
title_short	Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
title_full	Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
title_fullStr	Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
title_full_unstemmed	Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
title_sort	identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b54d5cf51ebf477bab841a9a57f9f31d
work_keys_str_mv	AT mirandayfong identificationofmetabolitesinthenormalovaryandtheirtransformationinprimaryandmetastaticovariancancer AT jonathanmcdunn identificationofmetabolitesinthenormalovaryandtheirtransformationinprimaryandmetastaticovariancancer AT shamskakar identificationofmetabolitesinthenormalovaryandtheirtransformationinprimaryandmetastaticovariancancer
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Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.

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