Division of Rheumatology, Department of Internal medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 03181 Seoul, Republic of Korea.
Department of Biotechnology, Graduate School, Korea University, 02841 Seoul, Republic of Korea.
Joint Bone Spine. 2018 May;85(3):337-343. doi: 10.1016/j.jbspin.2017.05.019. Epub 2017 May 24.
Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform.
Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HCs) were performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses.
A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (PLS-DA) model are RX of 0.246, RY of 0.913 and Q of 0.852, respectively, indicating strong explanation and prediction capabilities of the model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The PLS_DA model showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set.
This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS.
尽管许多白塞病(BD)的诊断标准已经被专家制定和修订,但诊断 BD 仍然很复杂和具有挑战性。尚未尝试对血清进行代谢组学研究,以改善诊断并确定 BD 的潜在生物标志物。本研究旨在探讨 BD 患者血清样本中独特的代谢变化,并使用代谢组学平台鉴定代谢候选生物标志物,以实现 BD 的可靠诊断。
通过气相色谱-飞行时间质谱(GC/TOF-MS)对 45 例 BD 患者和 45 例健康对照者(HCs)的 90 例血清样本进行代谢组学分析,并进行多变量统计分析。
从样本中鉴定出 104 种代谢物。GC/TOF-MS 分析获得的血清代谢谱可在发现集中区分 BD 患者和 HC 组。偏最小二乘判别分析(PLS-DA)模型的 RX、RY 和 Q 值分别为 0.246、0.913 和 0.852,表明模型具有较强的解释和预测能力。一组 5 种代谢标志物,即癸酸、果糖、塔格糖、亚油酸和油酸,被选择并在发现集中充分验证为 BD 的潜在生物标志物(灵敏度 100%,特异性 97.1%,曲线下面积 0.998)。PLS_DA 模型在独立集内通过 5 种代谢标志物清楚地区分了 BD 和 HC 组。
这是首次使用 GC/TOF-MS 报告可靠诊断 BD 的血清特征代谢谱和潜在代谢生物标志物。