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一种血浆脂质组学策略揭示了人类结直肠癌中脂质代谢途径的紊乱及潜在的脂质生物标志物。

A plasma lipidomics strategy reveals perturbed lipid metabolic pathways and potential lipid biomarkers of human colorectal cancer.

作者信息

Shen Sensen, Yang Li, Li Linnan, Bai Yu, Cai Chun, Liu Huwei

机构信息

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Institute of Analytical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.

Analytical Center, Guangdong Medical University, Zhanjiang, 524023, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Nov 15;1068-1069:41-48. doi: 10.1016/j.jchromb.2017.10.004. Epub 2017 Oct 4.

Abstract

To explore underlying molecular mechanisms and identify novel lipid biomarkers promising for colorectal cancer (CRC) diagnosis, a continuous-flow two dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (2D LC-QToF/MS) method was employed to comprehensively measure lipid species in human plasma of CRC patients and healthy controls. With a total of 427 annotated lipid species, we identified 64 lipid species with corrected p value less than 0.05 and fold change more than 1.5. These significantly altered lipid species were mainly involved in glycerolipids and glycerophospholipids metabolism and sphingolipids metabolism. After the diagnosis ability evaluation based on the receiver operating characteristic (ROC) curve, phosphatidylglycerol (34:0), sphingomyelin (42:2), ceramide (44:5), lysophosphatidylcholine (18:3), lysophosphatidylcholine (18:2), phosphatidylethanolamine (O-36:3), phosphatidylethanolamine (O-38:3) and sphingomyelin (38:8) were finally proposed as the potential biomarkers with the area under the curve (AUC) more than 0.900. These results suggest that this 2D LC-QToF/MS-based lipidomics profiling has great potential as a noninvasive diagnostic method in detecting CRC and hopefully provide new clues to understand its underlying mechanism.

摘要

为了探索潜在的分子机制并鉴定有望用于结直肠癌(CRC)诊断的新型脂质生物标志物,采用连续流二维液相色谱-四极杆飞行时间质谱(2D LC-QToF/MS)方法全面测定CRC患者和健康对照者血浆中的脂质种类。在总共427种注释的脂质种类中,我们鉴定出64种校正p值小于0.05且变化倍数大于1.5的脂质种类。这些显著改变的脂质种类主要参与甘油olipids和甘油磷脂代谢以及鞘脂代谢。基于受试者工作特征(ROC)曲线进行诊断能力评估后,最终提出磷脂酰甘油(34:0)、鞘磷脂(42:2)、神经酰胺(44:5)、溶血磷脂酰胆碱(18:3)、溶血磷脂酰胆碱(18:2)、磷脂酰乙醇胺(O-36:3)、磷脂酰乙醇胺(O-38:3)和鞘磷脂(38:8)作为曲线下面积(AUC)大于0.900的潜在生物标志物。这些结果表明,这种基于2D LC-QToF/MS的脂质组学分析作为一种检测CRC的非侵入性诊断方法具有巨大潜力,并有望为理解其潜在机制提供新线索。

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