Lipidome Alterations Induced by Cystic Fibrosis, CFTR Mutation, and Lung Function,Journal of Proteome Research

当前位置： X-MOL 学术 › J. Proteome Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Lipidome Alterations Induced by Cystic Fibrosis, CFTR Mutation, and Lung Function
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-10-22 , DOI: 10.1021/acs.jproteome.0c00556
Adriana Zardini Buzatto ₁ , Mai Abdel Jabar ₂ , Imran Nizami ₃ , Majed Dasouki ₂ , Liang Li ₁ , Anas M. Abdel Rahman _{2,

4,

5}

Affiliation

Cystic fibrosis is a genetic pathology characterized by abnormal accumulation of mucus in the respiratory, gastrointestinal, and reproductive tracts, caused by mutations in the CFTR gene. Although the classical presentation of the condition is well known, there is still a need for a better characterization of metabolic alterations related to cystic fibrosis and different genotypic mutations. We employed untargeted, comprehensive lipidomics of blood serum samples to investigate alterations in the lipid metabolism related to the pathology, mutation classes, and lung function decline. Six unique biomarker candidates were able to independently differentiate diseased individuals from healthy controls with excellent performance. Cystic fibrosis patients showed dyslipidemia for most lipid subclasses, with significantly elevated odd-chain and polyunsaturated fatty acyl lipids. Phosphatidic acids and diacylglycerols were particularly affected by different genotypic mutation classes. We selected a biomarker panel composed of four lipids, including two ceramides, one sphingomyelin, and one fatty acid, which correctly classified all validation samples from classes III and IV. A biomarker panel of five oxidized lipids was further selected to differentiate patients with reduced lung function, measured as predicted FEV1%. Our results indicate that cystic fibrosis is deeply related to lipid metabolism and provide new clues for the investigation of the disease mechanisms and therapeutic targets.

中文翻译：

囊性纤维化，CFTR突变和肺功能引起的脂质组改变

囊性纤维化是一种遗传病理学，其特征是CFTR突变引起呼吸道，胃肠道和生殖道中粘液异常积聚。基因。尽管该病的经典表现是众所周知的，但仍需要更好地表征与囊性纤维化和不同基因型突变有关的代谢变化。我们采用无针对性的，全面的血清样本脂质组学来研究与病理学，突变类别和肺功能下降相关的脂质代谢变化。六个独特的生物标志物候选物能够以出色的性能独立区分患病个体与健康对照。囊性纤维化患者大多数脂质亚类均显示血脂异常，其奇链和多不饱和脂肪酰基脂质明显升高。磷脂酸和二酰基甘油特别受不同基因型突变类别的影响。我们选择了由四种脂质组成的生物标志物组，其中包括两种神经酰胺，一种鞘磷脂和一种脂肪酸，它们可以正确分类所有来自III类和IV类的验证样品。进一步选择了由五种氧化脂质组成的生物标志物组，以区分肺功能降低的患者，以预测的FEV1％进行测量。我们的结果表明，囊性纤维化与脂质代谢密切相关，为研究疾病的机制和治疗靶点提供了新的线索。

更新日期：2020-10-22

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11