Abstract

Untargeted metabolomics is a well-established technique and a powerful tool to find potential plasma biomarkers for early diagnosing hereditary transthyretin amyloidosis. Hereditary transthyretin amyloidosis (ATTRv) is a disabling and fatal disease with different clinical features such as polyneuropathy, cardiomyopathy, different gastrointestinal symptoms and renal failure. Plasma specimens collected from 27 patients with ATTRv (ATTRV30M), 26 asymptomatic TTRV30M carriers and 26 control individuals were subjected to gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS)-based metabolomics analysis. Partial least squares discriminant and univariate analysis was used to analyse the data. The models constructed by Partial least squares-discriminant analysis (PLS-DA) could clearly discriminate ATTRV30M patients from controls and asymptomatic TTRV30M carriers. In total, 24 plasma metabolites (VIP > 1.0 and p < .05) were significantly altered in ATTRV30M patient group (6 increased and 18 decreased). Eleven of these distinguished the ATTRV30M group from both controls and TTRV30M carriers. Plasma metabolomics analysis revealed marked changes in several pathways in patients with ATTRV30M amyloidosis. Statistical analysis identified a panel of biomarkers that could effectively separate controls/TTRV30M carriers from ATTRV30M patients. These biomarkers can potentially be used to diagnose patients at an early stage of the disease.

摘要

非靶向代谢组学是一种成熟的技术，也是寻找潜在血浆生物标志物以早期诊断遗传性转甲状腺素蛋白淀粉样变性的有力工具。遗传性转甲状腺素蛋白淀粉样变性 (ATTRv) 是一种致残和致命的疾病，具有不同的临床特征，如多发性神经病、心肌病、不同的胃肠道症状和肾功能衰竭。从 27 名 ATTRv (ATTRV30M) 患者、26 名无症状TTR患者采集的血浆样本V30M 携带者和 26 名对照个体接受了基于气相色谱 (GC) 和液相色谱 (LC) 质谱 (MS) 的代谢组学分析。偏最小二乘判别和单变量分析用于分析数据。通过偏最小二乘判别分析 (PLS-DA) 构建的模型可以清楚地区分 ATTRV30M 患者与对照组和无症状TTR V30M 携带者。 ATTRV30M 患者组总共有 24 种血浆代谢物（VIP > 1.0 和p < .05）显着改变（6 增加，18 减少）。其中 11 个将 ATTRV30M 组与对照组和TTR区分开来V30M 运营商。血浆代谢组学分析显示 ATTRV30M 淀粉样变性患者的几种途径发生显着变化。统计分析确定了一组生物标志物，可以有效地将对照/ TTR V30M 携带者与 ATTRV30M 患者区分开来。这些生物标志物可以潜在地用于在疾病的早期诊断患者。