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首页> 外文期刊>Respiratory Research >Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis – a potential biomarker role for LysoPC
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Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis – a potential biomarker role for LysoPC

机译：血清代谢谱分析在特发性肺纤维化患者中发现了独特的代谢特征-LysoPC的潜在生物标志物作用

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BackgroundIdiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF. Metabolic signatures might indicate pathological pathways involved in disease development and progression. Reliable serum biomarker would help to improve both diagnostic approach and monitoring of drug effects. MethodThe global metabolic profiles measured by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy participants. The results were validated in an additional study of eleven IPF patients and ten healthy controls. ResultsWe discovered 10 discriminative metabolic features using multivariate and univariate statistical analysis. Among them, we identified one metabolite at a retention time of 9.59?min that was two times more abundant in the serum of IPF patients compared to healthy participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) – a known mediator for lung fibrosis with its pathway currently being evaluated as new therapeutic drug target for IPF and other fibrotic diseases. ConclusionsWe identified a LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF. Further validation studies in a larger cohort are necessary to determine its role in IPF. Trial RegistrationSerum samples from IPF patients have been obtained within the clinical trial NCT02173145 at baseline and from the idiopathic interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016–01524).
机译：背景特发性肺纤维化（IPF）是一种病因不明的致死性肺部疾病。患者表现出肺功能丧失，呼吸困难和干咳。诊断需要兼容的放射影像学检查，在不确定的情况下，需要进行侵入性检查，例如支气管镜检查和手术肺活检。 IPF的病理生理机制尚未完全了解。肺泡上皮修复异常的肺损伤被认为是IPF中纤维化途径激活的主要原因。代谢信号可能表明参与疾病发展和进展的病理途径。可靠的血清生物标志物将有助于改善诊断方法和药物效果监测。方法将超稳定液相色谱结合高分辨率质谱法（UHPLC-HRMS）对10例稳定IPF患者的总体代谢谱与10例健康参与者进行了比较。该结果在对11名IPF患者和10名健康对照者的另一项研究中得到了验证。结果我们使用多变量和单变量统计分析发现了10个区分性代谢特征。其中，我们鉴定出一种保留时间为9.59？min的代谢物，该代谢物在IPF患者血清中的含量是健康参与者的两倍。基于其离子图谱，提出了溶血磷脂酰胆碱（LysoPC）。 LysoPC是溶血磷脂酸（LPA）的前体-已知是肺纤维化的介质，其途径目前被评估为IPF和其他纤维化疾病的新治疗药物靶标。结论我们通过UHPLC-HRMS鉴定了LysoPC作为IPF患者血清中潜在的生物标志物。为了确定其在IPF中的作用，有必要在更大的队列中进行进一步的验证研究。试验注册从IPF患者的血清样本已在临床试验NCT02173145的基线和特发性间质性肺炎（IIP）队列研究中获得。该研究得到瑞士伦理委员会伯尔尼（KEK 002/14和246/15或PB_2016–01524）的批准。

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