Choline-phospholipids inter-conversion is altered in elderly patients with prostate cancer
Choline-phospholipids inter-conversion is altered in elderly patients with prostate cancer
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DOI：
10.1016/j.biochi.2016.01.003
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发表时间：
2016-07-01
期刊：
影响因子：
3.9
通讯作者：
Obeid, Rima
中科院分区：
文献类型：
--
作者：
Awwad, Hussain Mohamad;Ohlmann, Carsten-Henning;Obeid, Rima
背景：胆碱是哺乳动物细胞中磷脂和甲基的重要来源。恶性细胞对甲基和磷脂的高需求提示癌症患者胆碱代谢可能受到干扰。目的和方法：本病例对照研究调查了80例老年前列腺癌(PCa)患者和51例良性前列腺增生症(BPH)患者胆碱代谢产物浓度的差异。结果：游离胆碱、甜菜碱、二甲基甘氨酸、叶酸、总同型半胱氨酸、胱硫氨酸、甲基丙二酸、S-同型半胱氨酸、S-腺苷蛋氨酸和磷脂的浓度在前列腺增生症和前列腺癌患者中无显著差异(中位数分别为9.7mU/L和10.0mU/L)，叶酸(17.4nmol/L和19.8nmol/L)，tHcy(16.0mU/L)，L(18.8nmol/L)，和磷脂酰胆碱(1634vs.1610Mol/L)。前列腺癌患者的甲基丙二酸浓度较低(203比228nmol/L)，但在调整年龄后差异不显着。前列腺癌患者的鞘磷脂种类(16：0、18：0、18：1、20：0、22：0、22；1、23：0、23：1、24：0、24：1和24：2)显著低于对照组(6-16%)。多元回归分析显示PCa、他汀类药物使用、胆碱、年龄、胱硫氨酸和甲基丙二酸是神经鞘磷脂的显著负决定因素，而磷脂酰胆碱是强正决定因素。结论：本研究结果支持PCa磷脂代谢的全身性改变。我们报告了患有前列腺癌的老年患者和他汀类药物使用者的血浆鞘磷脂浓度显著降低。PCA相关的低鞘磷脂与他汀类药物有协同作用。PCA的存在与血浆胆碱或甲基代谢物浓度的显著变化无关。然而，在这项研究中不能排除胆碱吸收和组织摄取的变化。(C)2016年Elsevier B.V.和法国兴业银行(SFBBM)。版权所有。
Background: Choline is an important source of phospholipids and methyl groups in mammalian cells. High demands for methyl and phospholipids in malignant cells suggest that choline metabolism may be disturbed in patients with cancer.Objectives and Methods: This case-control study investigated differences in concentrations of choline metabolites between 80 elderly men (age >= 65 years) with prostate cancer (PCa) and 51 men with benign prostatic hyperplasia (BPH). Plasma/serum concentrations of free choline, betaine, dimethylglycine, folate, total homocysteine (tHcy), cystathionine, methylmalonic acid, S-adenosyl homocysteine (SAH), S-adenosyl methionine (SAM), and phospholipids were measured.Results: Men with BPH and those with PCa showed no significant differences in the concentrations of free choline (median = 9.7 vs. 10.0 mu mol/L), folate (17.4 vs. 19.8 nmol/L), tHcy (16.0 vs. 16.2 mu mol/L), SAH (18.8 vs. 18.2 nmol/L), and phosphatidylcholine (1634 vs. 1610 mu mol/L). The concentrations of methylmalonic acid were lower in men with PCa (203 vs. 228 nmol/L) but the difference was not significant after adjusting for age. Sphingomyelin species (16:0, 18:0, 18:1, 20:0, 22:0, 22; 1, 23:0, 23:1, 24:0, 24:1, and 24:2) were significantly lower in men with PCa than in the controls (6-16% differences). Multiple regression analyses showed that the presence of PCa, statin use, choline, age, cystathionine, and methylmalonic acid were significant negative determinant of sphingomyelins, whereas phosphatidylcholine was a strong positive determinant.Conclusions: The current results support systemic alterations in phospholipids metabolism in PCa. We report on a significant decrease in plasma concentrations of sphingomyelin in elderly patients with PCa and in users of statins. The PCa-associated low sphingomyelin showed a synergy with the effect of statins. The presence of PCa was not associated with significant changes in plasma concentrations of choline or methyl metabolites. However, changes in choline absorption and tissue uptake cannot be ruled out in this study. (C) 2016 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.