Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.
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鉴定正常卵巢中的代谢产物及其在原发性和转移性卵巢癌中的转化。
DOI：
10.1371/journal.pone.0019963
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kakar SS
中科院分区：
文献类型：
--
作者：
Fong MY;McDunn J;Kakar SS
在这项研究中，我们表征了人类卵巢的代谢组，并确定了与原发性上皮性卵巢癌（EOC）和原发性卵巢癌（MOC）导致的转移性肿瘤相一致的代谢变化，使用三种分析平台：气相色谱质谱（GC/MS）和液相色谱串联质谱（LC/MS/MS），使用缓冲系统和仪器设置来编目正离子或负离子。人类卵巢代谢组被发现含有364种生化物质，卵巢转化后引起能量利用的变化，改变了与糖酵解和脂肪酸β-氧化相关的代谢物，如肉毒碱。（EOC中为1.79倍，p<0.001; MOC中为1.88倍，p<0.001），乙酰卡尼汀001; MOC中2.39倍，p <0.001）和丁酰肉毒碱（EOC中3.62倍，p <0.0094; MOC中7.88倍，p<0.001）。在EOC中，苯丙氨酸催化剂也有显著变化，表现为苯丙酮酸（4.21倍; p =0.0098）和苯乳酸（195.45倍; p<0.0023）增加。 卵巢癌也显示出增强的氧化应激反应，如EOC（1.46倍，p = 0.0316）和MOC（2.25倍，p<0.001）中2-氨基丁酸和生育酚的几种亚型的增加所示。 我们还确定了卵巢中的新代谢物，特别是N-乙酰基谷氨酸和N-乙酰基-乙酰基谷氨酸，其在卵巢生理学中的作用尚未确定。这些数据增强了我们对人类卵巢生物化学多样性的理解，并证明了转化后的代谢改变。此外，代谢物组之间的显着变化提供了深入了解转化的生化后果，是卵巢肿瘤发生的候选生物标志物。验证研究是必要的，以确定这些化合物是否具有临床实用性，在卵巢癌患者的诊断或临床管理。
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.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
4
作者：
Fernandes, Carolina G.;Leipnitz, Guilhian;Wajner, Moacir
通讯作者：
Wajner, Moacir
影响因子：
2.6
作者：
Frickenschmidt, Antje;Froehlich, Holger;Kammerer, Bernd
通讯作者：
Kammerer, Bernd
影响因子：
4.4
作者：
Chan, Eric Chun Yong;Koh, Poh Koon;Keun, Hector C.
通讯作者：
Keun, Hector C.