Djekic Demir, Pinto Rui, Vorkas Panagiotis A, Henein Michael Y
Department of Public Health and Clinical Medicine, Umeå University And Heart Centre, Umeå, Sweden.
Computational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden; Bioinformatics for Life Sciences (BILS), Sweden.
Int J Cardiol. 2016 Nov 1;222:1042-1048. doi: 10.1016/j.ijcard.2016.07.214. Epub 2016 Aug 2.
Recently a lipidomics approach was able to identify perturbed fatty acyl chain (FAC) and sphingolipid moieties that could stratify patients according to the severity of coronary calcification, a form of subclinical atherosclerosis. Nevertheless, these findings have not yet been reproduced before generalising their application. The aim of this study was to evaluate the reproducibility of lipidomics approaches by replicating previous lipidomic findings in groups of patients with calcific coronary artery disease (CCAD).
Patients were separated into the following groups based on their calcium score (CS); no calcification (CS: 0; n=26), mild calcification (CS: 1-250; n=27) and severe calcification (CS: >250; n=17). Two serum samples were collected from each patient and used for comparative analyses by 2 different laboratories, in different countries and time points using liquid chromatography coupled to mass spectrometry untargeted lipidomics methods.
Six identical metabolites differentiated patients with severe coronary artery calcification from those with no calcification were found by both laboratories independently. Additionally, relative intensities from the two analyses demonstrated high correlation coefficients. Phosphatidylcholine moieties with 18-carbon FAC were identified in lower intensities and 20:4 FAC in higher intensities in the serum of diseased group. Moreover, 3 common sphingomyelins were detected.
This is the first interlaboratory reproducibility study utilising lipidomics applications in general and specifically in patients with CCAD. Lipid profiling applications in patients with CCAD are very reproducible in highly specialised and experienced laboratories and could be applied in clinical practice in order to spare patients diagnostic radiation.
最近，一种脂质组学方法能够识别出受干扰的脂肪酰链（FAC）和鞘脂部分，这些成分可根据冠状动脉钙化（一种亚临床动脉粥样硬化形式）的严重程度对患者进行分层。然而，在推广其应用之前，这些发现尚未得到重复验证。本研究的目的是通过在钙化性冠状动脉疾病（CCAD）患者组中重复先前的脂质组学研究结果，评估脂质组学方法的可重复性。
根据患者的钙评分（CS）将患者分为以下几组：无钙化（CS：0；n = 26）、轻度钙化（CS：1 - 250；n = 27）和重度钙化（CS：> 250；n = 17）。从每位患者收集两份血清样本，并由不同国家和不同时间点的两个不同实验室使用液相色谱 - 质谱联用非靶向脂质组学方法进行比较分析。
两个实验室独立发现了六种相同的代谢物，可区分重度冠状动脉钙化患者和无钙化患者。此外，两次分析的相对强度显示出高相关系数。在患病组血清中，含有18碳FAC的磷脂酰胆碱部分强度较低，而20:4 FAC强度较高。此外，还检测到3种常见的鞘磷脂。
这是第一项利用脂质组学应用进行的实验室间可重复性研究，特别是针对CCAD患者。在高度专业化和经验丰富的实验室中，CCAD患者的脂质谱分析应用具有很高的可重复性，可应用于临床实践，以避免患者接受诊断性辐射。
